16 results on '"Chandra, Dhyan"'
Search Results
2. Targeting the mitochondrial unfolded protein response in cancer: opportunities and challenges
- Author
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Inigo, Joseph R., Kumar, Rahul, and Chandra, Dhyan
- Abstract
Increasing evidence indicates that a mitochondria-specific stress response referred to as the ‘mitochondrial unfolded protein response’ (UPRmt) is activated to maintain mitochondrial integrity and support tumor growth. In this forum article, we discuss the recent advances and current challenges in therapeutically targeting UPRmtin cancer.
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- 2021
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3. Mitochondrial Stress Response and Cancer
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O’Malley, Jordan, Kumar, Rahul, Inigo, Joseph, Yadava, Nagendra, and Chandra, Dhyan
- Abstract
Cancer cells survive and adapt to many types of stress including hypoxia, nutrient deprivation, metabolic, and oxidative stress. These stresses are sensed by diverse cellular signaling processes, leading to either degradation of mitochondria or alleviation of mitochondrial stress. This review discusses signaling during sensing and mitigation of stress involving mitochondrial communication with the endoplasmic reticulum, and how retrograde signaling upregulates the mitochondrial stress response to maintain mitochondrial integrity. The importance of the mitochondrial unfolded protein response, an emerging pathway that alleviates cellular stress, will be elaborated with respect to cancer. Detailed understanding of cellular pathways will establish mitochondrial stress response as a key mechanism for cancer cell survival leading to cancer progression and resistance, and provide a potential therapeutic target in cancer.
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- 2020
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4. Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy.
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Cheruku, Ravindra R., Cacaccio, Joseph, Durrani, Farukh A., Tabaczynski, Walter A., Watson, Ramona, Marko, Aimee, Kumar, Rahul, El-Khouly, Mohamed E., Fukuzumi, Shunichi, Missert, Joseph R., Yao, Rutao, Sajjad, Munawwar, Chandra, Dhyan, Guru, Khurshid, and Pandey, Ravindra K.
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- 2019
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5. Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy
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Cheruku, Ravindra R., Cacaccio, Joseph, Durrani, Farukh A., Tabaczynski, Walter A., Watson, Ramona, Marko, Aimee, Kumar, Rahul, El-Khouly, Mohamed E., Fukuzumi, Shunichi, Missert, Joseph R., Yao, Rutao, Sajjad, Munawwar, Chandra, Dhyan, Guru, Khurshid, and Pandey, Ravindra K.
- Abstract
The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3and 5showed EGFR target specificity, but the position-3 erlotinib–PS conjugate 3demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS–erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to 18F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (124I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 μCi/mouse.
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- 2019
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6. Combination therapy induces unfolded protein response and cytoskeletal rearrangement leading to mitochondrial apoptosis in prostate cancer.
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Kumar, Sandeep, Chaudhary, Ajay K., Kumar, Rahul, O'Malley, Jordan, Dubrovska, Anna, Wang, Xinjiang, Yadav, Neelu, Goodrich, David W., and Chandra, Dhyan
- Abstract
Development of therapeutic resistance is responsible for most prostate cancer (PCa) related mortality. Resistance has been attributed to an acquired or selected cancer stem cell phenotype. Here we report the histone deacetylase inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel (TXL)-induced apoptosis in PCa cells and limit accumulation of cancer stem cells. TXL-induced responses were modulated in the presence of TG with increased accumulation of cells at G1-phase, rearrangement of the cytoskeleton, and changes in cytokine release. Cytoskeletal rearrangement was associated with modulation of the cytoplasmic and mitochondrial unfolded protein response leading to mitochondrial dysfunction and release of proapoptotic proteins from mitochondria. TXL in combination with APC or TG enhanced caspase activation. Importantly, TXL in combination with TG induced caspase activation and apoptosis in X-ray resistant LNCaP cells. Increased release of transforming growth factor-beta (TGF-β) was observed while phosphorylated β-catenin level was suppressed with TXL combination treatments. This was accompanied by a decrease in the CD44 + CD133 + cancer stem cell-like population, suggesting treatment affects cancer stem cell properties. Taken together, combination treatment with TXL and either APC or TG induces efficient apoptosis in both proliferating and cancer stem cells, suggesting this therapeutic combination may overcome drug resistance and recurrence in PCa. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Effects of anti-cancer drug doxorubicin on endogenous biomarkers NAD(P)H, FAD and Trp in prostate cancer cells: a FLIM Study
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Periasamy, Ammasi, So, Peter T. C., König, Karsten, Xie, Xiaoliang S., Rehman Alam, Shagufta, Wallrabe, Horst, Svindrych, Zdenek, Christopher, Kathryn G., Chandra, Dhyan, and Periasamy, Ammasi
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- 2017
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8. Investigation of prostate cancer cells using NADH and Tryptophan as biomarker: multiphoton FLIM-FRET microscopy
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Periasamy, Ammasi, So, Peter T. C., König, Karsten, Rehman, Shagufta, O'Melia, Meghan J., Wallrabe, Horst, Svindrych, Zdenek, Chandra, Dhyan, and Periasamy, Ammasi
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- 2016
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9. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
- Author
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Klionsky, Daniel J, Abdelmohsen, Kotb, Abe, Akihisa, Abedin, Md Joynal, Abeliovich, Hagai, Acevedo Arozena, Abraham, Adachi, Hiroaki, Adams, Christopher M, Adams, Peter D, Adeli, Khosrow, Adhihetty, Peter J, Adler, Sharon G, Agam, Galila, Agarwal, Rajesh, Aghi, Manish K, Agnello, Maria, Agostinis, Patrizia, Aguilar, Patricia V, Aguirre-Ghiso, Julio, Airoldi, Edoardo M, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akporiaye, Emmanuel T, Al-Rubeai, Mohamed, Albaiceta, Guillermo M, Albanese, Chris, Albani, Diego, Albert, Matthew L, Aldudo, Jesus, Algül, Hana, Alirezaei, Mehrdad, Alloza, Iraide, Almasan, Alexandru, Almonte-Beceril, Maylin, Alnemri, Emad S, Alonso, Covadonga, Altan-Bonnet, Nihal, Altieri, Dario C, Alvarez, Silvia, Alvarez-Erviti, Lydia, Alves, Sandro, Amadoro, Giuseppina, Amano, Atsuo, Amantini, Consuelo, Ambrosio, Santiago, Amelio, Ivano, Amer, Amal O, Amessou, Mohamed, Amon, Angelika, An, Zhenyi, Anania, Frank A, Andersen, Stig U, Andley, Usha P, Andreadi, Catherine K, Andrieu-Abadie, Nathalie, Anel, Alberto, Ann, David K, Anoopkumar-Dukie, Shailendra, Antonioli, Manuela, Aoki, Hiroshi, Apostolova, Nadezda, Aquila, Saveria, Aquilano, Katia, Araki, Koichi, Arama, Eli, Aranda, Agustin, Araya, Jun, Arcaro, Alexandre, Arias, Esperanza, Arimoto, Hirokazu, Ariosa, Aileen R, Armstrong, Jane L, Arnould, Thierry, Arsov, Ivica, Asanuma, Katsuhiko, Askanas, Valerie, Asselin, Eric, Atarashi, Ryuichiro, Atherton, Sally S, Atkin, Julie D, Attardi, Laura D, Auberger, Patrick, Auburger, Georg, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Avantaggiati, Maria Laura, Avrahami, Limor, Awale, Suresh, Azad, Neelam, Bachetti, Tiziana, Backer, Jonathan M, Bae, Dong-Hun, Bae, Jae-sung, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H, Baek, Seung-Hoon, Baghdiguian, Stephen, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xue-Yuan, Bailly, Yannick, Balaji, Kithiganahalli Narayanaswamy, Balduini, Walter, Ballabio, Andrea, Balzan, Rena, Banerjee, Rajkumar, Bánhegyi, Gábor, Bao, Haijun, Barbeau, Benoit, Barrachina, Maria D, Barreiro, Esther, Bartel, Bonnie, Bartolomé, Alberto, Bassham, Diane C, Bassi, Maria Teresa, Bast, Robert C, Basu, Alakananda, Batista, Maria Teresa, Batoko, Henri, Battino, Maurizio, Bauckman, Kyle, Baumgarner, Bradley L, Bayer, K Ulrich, Beale, Rupert, Beaulieu, Jean-François, Beck, George R., Becker, Christoph, Beckham, J David, Bédard, Pierre-André, Bednarski, Patrick J, Begley, Thomas J, Behl, Christian, Behrends, Christian, Behrens, Georg MN, Behrns, Kevin E, Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Bénard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amélie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S, Besteiro, Sébastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K, Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W, Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A, Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Böckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H, Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jürgen, Botana, Luis M, Botti, Joelle, Bou, German, Bouché, Marina, Bouchecareilh, Marion, Boucher, Marie-Josée, Boulton, Michael E, Bouret, Sebastien G, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan, Braga, Vania MM, Brancolini, Claudio, Braus, Gerhard H, Bravo-San Pedro, José M, Brennan, Lisa A, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bringer, Marie-Agnès, Brini, Marisa, Brito, Glauber C, Brodin, Bertha, Brookes, Paul S, Brown, Eric J, Brown, Karen, Broxmeyer, Hal E, Bruhat, Alain, Brum, Patricia Chakur, Brumell, John H, Brunetti-Pierri, Nicola, Bryson-Richardson, Robert J, Buch, Shilpa, Buchan, Alastair M, Budak, Hikmet, Bulavin, Dmitry V, Bultman, Scott J, Bultynck, Geert, Bumbasirevic, Vladimir, Burelle, Yan, Burke, Robert E, Burmeister, Margit, Bütikofer, Peter, Caberlotto, Laura, Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jingjing, Cai, Qian, Calatayud, Sara, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Grant R, Campbell, Matthew, Campello, Silvia, Candau, Robin, Caniggia, Isabella, Cantoni, Lavinia, Cao, Lizhi, Caplan, Allan B, Caraglia, Michele, Cardinali, Claudio, Cardoso, Sandra Morais, Carew, Jennifer S, Carleton, Laura A, Carlin, Cathleen R, Carloni, Silvia, Carlsson, Sven R, Carmona-Gutierrez, Didac, Carneiro, Leticia AM, Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I, Ceña, Valentín, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S, Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond YW, Chan, Matthew TV, Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C, Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E, Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W, Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher HK, Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi NC, Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C, Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine MK, Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E, Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T, Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A, Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J, Clària, Joan, Clarke, Peter GH, Clarke, Robert, Clementi, Emilio, Cleyrat, Cédric, Cnop, Miriam, Coccia, Eliana M, Cocco, Tiziana, Codogno, Patrice, Coers, Jörn, Cohen, Ezra EW, Colecchia, David, Coletto, Luisa, Coll, Núria S, Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L, Coombs, Graham H, Cooper, Cynthia D, Cooper, J Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D, Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Cotman, Susan L, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R, Cowart, L Ashley, Cox, Jeffery S, Coxon, Fraser P, Coyne, Carolyn B, Cragg, Mark S, Craven, Rolf J, Crepaldi, Tiziana, Crespo, Jose L, Criollo, Alfredo, Crippa, Valeria, Cruz, Maria Teresa, Cuervo, Ana Maria, Cuezva, Jose M, Cui, Taixing, Cutillas, Pedro R, Czaja, Mark J, Czyzyk-Krzeska, Maria F, Dagda, Ruben K, Dahmen, Uta, Dai, Chunsun, Dai, Wenjie, Dai, Yun, Dalby, Kevin N, Dalla Valle, Luisa, Dalmasso, Guillaume, D'Amelio, Marcello, Damme, Markus, Darfeuille-Michaud, Arlette, Dargemont, Catherine, Darley-Usmar, Victor M, Dasarathy, Srinivasan, Dasgupta, Biplab, Dash, Srikanta, Dass, Crispin R, Davey, Hazel Marie, Davids, Lester M, Dávila, David, Davis, Roger J, Dawson, Ted M, Dawson, Valina L, Daza, Paula, de Belleroche, Jackie, de Figueiredo, Paul, de Figueiredo, Regina Celia Bressan Queiroz, de la Fuente, José, De Martino, Luisa, De Matteis, Antonella, De Meyer, Guido RY, De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P, Delage-Mourroux, Régis, Delbridge, Lea MD, Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J, Deretic, Vojo, Derrien, Benoît, Deutsch, Eric, Devarenne, Timothy P, Devenish, Rodney J, Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Díaz-Araya, Guillermo, Díaz-Laviada, Ines, Diaz-Meco, Maria T, Diaz-Nido, Javier, Dickey, Chad A, Dickson, Robert C, Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P, Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Jörg HW, Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick CJ, Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M, Doran, Kelly S, D'Orazi, Gabriella, Dorn, Gerald W, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, André, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R, Duchosal, Michel A, Duez, Helene, Dugail, Isabelle, Dumit, Verónica I, Duncan, Mara C, Dunlop, Elaine A, Dunn, William A, Dupont, Nicolas, Dupuis, Luc, Durán, Raúl V, Durcan, Thomas M, Duvezin-Caubet, Stéphane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L, Edinger, Aimee L, Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N Tony, El-Deiry, Wafik S, El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris JH, Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelender, Simone, Enserink, Jorrit M, Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L, Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva-Liisa, Espert, Lucile, Esteban-Martínez, Lorena, Evans, Thomas J, Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Færgeman, Nils J, Faggioni, Alberto, Fairlie, W Douglas, Fan, Chunhai, Fan, Daping, Fan, Jie, Fang, Shengyun, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Faure, Mathias, Favier, Francois B, Fearnhead, Howard, Federici, Massimo, Fei, Erkang, Felizardo, Tania C, Feng, Hua, Feng, Yibin, Feng, Yuchen, Ferguson, Thomas A, Fernández, Álvaro F, Fernandez-Barrena, Maite G, Fernandez-Checa, Jose C, Fernández-López, Arsenio, Fernandez-Zapico, Martin E, Feron, Olivier, Ferraro, Elisabetta, Ferreira-Halder, Carmen Veríssima, Fesus, Laszlo, Feuer, Ralph, Fiesel, Fabienne C, Filippi-Chiela, Eduardo C, Filomeni, Giuseppe, Fimia, Gian Maria, Fingert, John H, Finkbeiner, Steven, Finkel, Toren, Fiorito, Filomena, Fisher, Paul B, Flajolet, Marc, Flamigni, Flavio, Florey, Oliver, Florio, Salvatore, Floto, R Andres, Folini, Marco, Follo, Carlo, Fon, Edward A, Fornai, Francesco, Fortunato, Franco, Fraldi, Alessandro, Franco, Rodrigo, Francois, Arnaud, François, Aurélie, Frankel, Lisa B, Fraser, Iain DC, Frey, Norbert, Freyssenet, Damien G, Frezza, Christian, Friedman, Scott L, Frigo, Daniel E, Fu, Dongxu, Fuentes, José M, Fueyo, Juan, Fujitani, Yoshio, Fujiwara, Yuuki, Fujiya, Mikihiro, Fukuda, Mitsunori, Fulda, Simone, Fusco, Carmela, Gabryel, Bozena, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galadari, Sehamuddin, Galili, Gad, Galindo, Inmaculada, Galindo, Maria F, Galliciotti, Giovanna, Galluzzi, Lorenzo, Galluzzi, Luca, Galy, Vincent, Gammoh, Noor, Gandy, Sam, Ganesan, Anand K, Ganesan, Swamynathan, Ganley, Ian G, Gannagé, Monique, Gao, Fen-Biao, Gao, Feng, Gao, Jian-Xin, García Nannig, Lorena, García Véscovi, Eleonora, Garcia-Macía, Marina, Garcia-Ruiz, Carmen, Garg, Abhishek D, Garg, Pramod Kumar, Gargini, Ricardo, Gassen, Nils Christian, Gatica, Damián, Gatti, Evelina, Gavard, Julie, Gavathiotis, Evripidis, Ge, Liang, Ge, Pengfei, Ge, Shengfang, Gean, Po-Wu, Gelmetti, Vania, Genazzani, Armando A, Geng, Jiefei, Genschik, Pascal, Gerner, Lisa, Gestwicki, Jason E, Gewirtz, David A, Ghavami, Saeid, Ghigo, Eric, Ghosh, Debabrata, Giammarioli, Anna Maria, Giampieri, Francesca, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibbings, Derrick J, Gibellini, Lara, Gibson, Spencer B, Ginet, Vanessa, Giordano, Antonio, Giorgini, Flaviano, Giovannetti, Elisa, Girardin, Stephen E, Gispert, Suzana, Giuliano, Sandy, Gladson, Candece L, Glavic, Alvaro, Gleave, Martin, Godefroy, Nelly, Gogal, Robert M, Gokulan, Kuppan, Goldman, Gustavo H, Goletti, Delia, Goligorsky, Michael S, Gomes, Aldrin V, Gomes, Ligia C, Gomez, Hernando, Gomez-Manzano, Candelaria, Gómez-Sánchez, Rubén, Gonçalves, Dawit AP, Goncu, Ebru, Gong, Qingqiu, Gongora, Céline, Gonzalez, Carlos B, Gonzalez-Alegre, Pedro, Gonzalez-Cabo, Pilar, González-Polo, Rosa Ana, Goping, Ing Swie, Gorbea, Carlos, Gorbunov, Nikolai V, Goring, Daphne R, Gorman, Adrienne M, Gorski, Sharon M, Goruppi, Sandro, Goto-Yamada, Shino, Gotor, Cecilia, Gottlieb, Roberta A, Gozes, Illana, Gozuacik, Devrim, Graba, Yacine, Graef, Martin, Granato, Giovanna E, Grant, Gary Dean, Grant, Steven, Gravina, Giovanni Luca, Green, Douglas R, Greenhough, Alexander, Greenwood, Michael T, Grimaldi, Benedetto, Gros, Frédéric, Grose, Charles, Groulx, Jean-Francois, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Guan, Jun-Lin, Guan, Kun-Liang, Guerra, Barbara, Guillen, Carlos, Gulshan, Kailash, Gunst, Jan, Guo, Chuanyong, Guo, Lei, Guo, Ming, Guo, Wenjie, Guo, Xu-Guang, Gust, Andrea A, Gustafsson, Åsa B, Gutierrez, Elaine, Gutierrez, Maximiliano G, Gwak, Ho-Shin, Haas, Albert, Haber, James E, Hadano, Shinji, Hagedorn, Monica, Hahn, David R, Halayko, Andrew J, Hamacher-Brady, Anne, Hamada, Kozo, Hamai, Ahmed, Hamann, Andrea, Hamasaki, Maho, Hamer, Isabelle, Hamid, Qutayba, Hammond, Ester M, Han, Feng, Han, Weidong, Handa, James T, Hanover, John A, Hansen, Malene, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Harper, J Wade, Harrath, Abdel Halim, Harris, Adrian L, Harris, James, Hasler, Udo, Hasselblatt, Peter, Hasui, Kazuhisa, Hawley, Robert G, Hawley, Teresa S, He, Congcong, He, Cynthia Y, He, Fengtian, He, Gu, He, Rong-Rong, He, Xian-Hui, He, You-Wen, He, Yu-Ying, Heath, Joan K, Hébert, Marie-Josée, Heinzen, Robert A, Helgason, Gudmundur Vignir, Hensel, Michael, Henske, Elizabeth P, Her, Chengtao, Herman, Paul K, Hernández, Agustín, Hernandez, Carlos, Hernández-Tiedra, Sonia, Hetz, Claudio, Hiesinger, P Robin, Higaki, Katsumi, Hilfiker, Sabine, Hill, Bradford G, Hill, Joseph A, Hill, William D, Hino, Keisuke, Hofius, Daniel, Hofman, Paul, Höglinger, Günter U, Höhfeld, Jörg, Holz, Marina K, Hong, Yonggeun, Hood, David A, Hoozemans, Jeroen JM, Hoppe, Thorsten, Hsu, Chin, Hsu, Chin-Yuan, Hsu, Li-Chung, Hu, Dong, Hu, Guochang, Hu, Hong-Ming, Hu, Hongbo, Hu, Ming Chang, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Ya, Huang, Canhua, Huang, Huey-Lan, Huang, Kuo-How, Huang, Kuo-Yang, Huang, Shile, Huang, Shiqian, Huang, Wei-Pang, Huang, Yi-Ran, Huang, Yong, Huang, Yunfei, Huber, Tobias B, Huebbe, Patricia, Huh, Won-Ki, Hulmi, Juha J, Hur, Gang Min, Hurley, James H, Husak, Zvenyslava, Hussain, Sabah NA, Hussain, Salik, Hwang, Jung Jin, Hwang, Seungmin, Hwang, Thomas IS, Ichihara, Atsuhiro, Imai, Yuzuru, Imbriano, Carol, Inomata, Megumi, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L, Iozzo, Renato V, Ip, Nancy Y, Irazoqui, Javier E, Iribarren, Pablo, Isaka, Yoshitaka, Isakovic, Aleksandra J, Ischiropoulos, Harry, Isenberg, Jeffrey S, Ishaq, Mohammad, Ishida, Hiroyuki, Ishii, Isao, Ishmael, Jane E, Isidoro, Ciro, Isobe, Ken-ichi, Isono, Erika, Issazadeh-Navikas, Shohreh, Itahana, Koji, Itakura, 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Sikorska, Beata, Silveira, Wilian A, Silvente-Poirot, Sandrine, Silverman, Gary A, Simak, Jan, Simmet, Thomas, Simon, Anna Katharina, Simon, Hans-Uwe, Simone, Cristiano, Simons, Matias, Simonsen, Anne, Singh, Rajat, Singh, Shivendra V, Singh, Shrawan K, Sinha, Debasish, Sinha, Sangita, Sinicrope, Frank A, Sirko, Agnieszka, Sirohi, Kapil, Sishi, Balindiwe JN, Sittler, Annie, Siu, Parco M, Sivridis, Efthimios, Skwarska, Anna, Slack, Ruth, Slaninová, Iva, Slavov, Nikolai, Smaili, Soraya S, Smalley, Keiran SM, Smith, Duncan R, Soenen, Stefaan J, Soleimanpour, Scott A, Solhaug, Anita, Somasundaram, Kumaravel, Son, Jin H, Sonawane, Avinash, Song, Chunjuan, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Wei, Soo, Kai Y, Sood, Anil K, Soong, Tuck Wah, Soontornniyomkij, Virawudh, Sorice, Maurizio, Sotgia, Federica, Soto-Pantoja, David R, Sotthibundhu, Areechun, Sousa, Maria João, Spaink, Herman P, Span, Paul N, Spang, Anne, Sparks, Janet D, Speck, Peter G, Spector, Stephen A, Spies, Claudia D, Springer, Wolfdieter, Clair, Daret St, Stacchiotti, Alessandra, Staels, Bart, Stang, Michael T, Starczynowski, Daniel T, Starokadomskyy, Petro, Steegborn, Clemens, Steele, John W, Stefanis, Leonidas, Steffan, Joan, Stellrecht, Christine M, Stenmark, Harald, Stepkowski, Tomasz M, Stern, Stęphan T, Stevens, Craig, Stockwell, Brent R, Stoka, Veronika, Storchova, Zuzana, Stork, Björn, Stratoulias, Vassilis, Stravopodis, Dimitrios J, Strnad, Pavel, Strohecker, Anne Marie, Ström, Anna-Lena, Stromhaug, Per, Stulik, Jiri, Su, Yu-Xiong, Su, Zhaoliang, Subauste, Carlos S, Subramaniam, Srinivasa, Sue, Carolyn M, Suh, Sang Won, Sui, Xinbing, Sukseree, Supawadee, Sulzer, David, Sun, Fang-Lin, Sun, Jiaren, Sun, Jun, Sun, Shi-Yong, Sun, Yang, Sun, Yi, Sun, Yingjie, Sundaramoorthy, Vinod, Sung, Joseph, Suzuki, Hidekazu, Suzuki, Kuninori, Suzuki, Naoki, Suzuki, Tadashi, Suzuki, Yuichiro J, Swanson, Michele S, Swanton, Charles, Swärd, Karl, Swarup, Ghanshyam, Sweeney, Sean T, Sylvester, Paul W, Szatmari, Zsuzsanna, Szegezdi, Eva, Szlosarek, Peter W, Taegtmeyer, Heinrich, Tafani, Marco, Taillebourg, Emmanuel, Tait, Stephen WG, Takacs-Vellai, Krisztina, Takahashi, Yoshinori, Takáts, Szabolcs, Takemura, Genzou, Takigawa, Nagio, Talbot, Nicholas J, Tamagno, Elena, Tamburini, Jerome, Tan, Cai-Ping, Tan, Lan, Tan, Mei Lan, Tan, Ming, Tan, Yee-Joo, Tanaka, Keiji, Tanaka, Masaki, Tang, Daolin, Tang, Dingzhong, Tang, Guomei, Tanida, Isei, Tanji, Kunikazu, Tannous, Bakhos A, Tapia, Jose A, Tasset-Cuevas, Inmaculada, Tatar, Marc, Tavassoly, Iman, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Graham S, Taylor, Gregory A, Taylor, J Paul, Taylor, Mark J, Tchetina, Elena V, Tee, Andrew R, Teixeira-Clerc, Fatima, Telang, Sucheta, Tencomnao, Tewin, Teng, Ba-Bie, Teng, Ru-Jeng, Terro, Faraj, Tettamanti, Gianluca, Theiss, Arianne L, Theron, Anne E, Thomas, Kelly Jean, Thomé, Marcos P, Thomes, Paul G, Thorburn, Andrew, Thorner, Jeremy, Thum, Thomas, Thumm, Michael, Thurston, Teresa LM, Tian, Ling, Till, Andreas, Ting, Jenny Pan-yun, Titorenko, Vladimir I, Toker, Lilach, Toldo, Stefano, Tooze, Sharon A, Topisirovic, Ivan, Torgersen, Maria Lyngaas, Torosantucci, Liliana, Torriglia, Alicia, Torrisi, Maria Rosaria, Tournier, Cathy, Towns, Roberto, Trajkovic, Vladimir, Travassos, Leonardo H, Triola, Gemma, Tripathi, Durga Nand, Trisciuoglio, Daniela, Troncoso, Rodrigo, Trougakos, Ioannis P, Truttmann, Anita C, Tsai, Kuen-Jer, Tschan, Mario P, Tseng, Yi-Hsin, Tsukuba, Takayuki, Tsung, Allan, Tsvetkov, Andrey S, Tu, Shuiping, Tuan, Hsing-Yu, Tucci, Marco, Tumbarello, David A, Turk, Boris, Turk, Vito, Turner, Robin FB, Tveita, Anders A, Tyagi, Suresh C, Ubukata, Makoto, Uchiyama, Yasuo, Udelnow, Andrej, Ueno, Takashi, Umekawa, Midori, Umemiya-Shirafuji, Rika, Underwood, Benjamin R, Ungermann, Christian, Ureshino, Rodrigo P., Ushioda, Ryo, Uversky, Vladimir N, Uzcátegui, Néstor L, Vaccari, Thomas, Vaccaro, Maria I, Váchová, Libuše, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Enza Maria, Vallette, Francois, Valverde, Angela M, Van den Berghe, Greet, Van Den Bosch, Ludo, van den Brink, Gijs R, van der Goot, F Gisou, van der Klei, Ida J, van der Laan, Luc JW, van Doorn, Wouter G, van Egmond, Marjolein, van Golen, Kenneth L, Van Kaer, Luc, van Lookeren Campagne, Menno, Vandenabeele, Peter, Vandenberghe, Wim, Vanhorebeek, Ilse, Varela-Nieto, Isabel, Vasconcelos, M Helena, Vasko, Radovan, Vavvas, Demetrios G, Vega-Naredo, Ignacio, Velasco, Guillermo, Velentzas, Athanassios D, Velentzas, Panagiotis D, Vellai, Tibor, Vellenga, Edo, Vendelbo, Mikkel Holm, Venkatachalam, Kartik, Ventura, Natascia, Ventura, Salvador, Veras, Patrícia ST, Verdier, Mireille, Vertessy, Beata G, Viale, Andrea, Vidal, Michel, Vieira, Helena LA, Vierstra, Richard D, Vigneswaran, Nadarajah, Vij, Neeraj, Vila, Miquel, Villar, Margarita, Villar, Victor H, Villarroya, Joan, Vindis, Cécile, Viola, Giampietro, Viscomi, Maria Teresa, Vitale, Giovanni, Vogl, Dan T, Voitsekhovskaja, Olga V, von Haefen, Clarissa, von Schwarzenberg, Karin, Voth, Daniel E, Vouret-Craviari, Valérie, Vuori, Kristina, Vyas, Jatin M, Waeber, Christian, Walker, Cheryl Lyn, Walker, Mark J, Walter, Jochen, Wan, Lei, Wan, Xiangbo, Wang, Bo, Wang, Caihong, Wang, Chao-Yung, Wang, Chengshu, Wang, Chenran, Wang, Chuangui, Wang, Dong, Wang, Fen, Wang, Fuxin, Wang, Guanghui, Wang, Hai-jie, Wang, Haichao, Wang, Hong-Gang, Wang, Hongmin, Wang, Horng-Dar, Wang, Jing, Wang, Junjun, Wang, Mei, Wang, Mei-Qing, Wang, Pei-Yu, Wang, Peng, Wang, Richard C, Wang, Shuo, Wang, Ting-Fang, Wang, Xian, Wang, Xiao-jia, Wang, Xiao-Wei, Wang, Xin, Wang, Xuejun, Wang, Yan, Wang, Yanming, Wang, Ying, Wang, Ying-Jan, Wang, Yipeng, Wang, Yu, Wang, Yu Tian, Wang, Yuqing, Wang, Zhi-Nong, Wappner, Pablo, Ward, Carl, Ward, Diane McVey, Warnes, Gary, Watada, Hirotaka, Watanabe, Yoshihisa, Watase, Kei, Weaver, Timothy E, Weekes, Colin D, Wei, Jiwu, Weide, Thomas, Weihl, Conrad C, Weindl, Günther, Weis, Simone Nardin, Wen, Longping, Wen, Xin, Wen, Yunfei, Westermann, Benedikt, Weyand, Cornelia M, White, Anthony R, White, Eileen, Whitton, J Lindsay, Whitworth, Alexander J, Wiels, Joëlle, Wild, Franziska, Wildenberg, Manon E, Wileman, Tom, Wilkinson, Deepti Srinivas, Wilkinson, Simon, Willbold, Dieter, Williams, Chris, Williams, Katherine, Williamson, Peter R, Winklhofer, Konstanze F, Witkin, Steven S, Wohlgemuth, Stephanie E, Wollert, Thomas, Wolvetang, Ernst J, Wong, Esther, Wong, G William, Wong, Richard W, Wong, Vincent Kam Wai, Woodcock, Elizabeth A, Wright, Karen L, Wu, Chunlai, Wu, Defeng, Wu, Gen Sheng, Wu, Jian, Wu, Junfang, Wu, Mian, Wu, Min, Wu, Shengzhou, Wu, William KK, Wu, Yaohua, Wu, Zhenlong, Xavier, Cristina PR, Xavier, Ramnik J, Xia, Gui-Xian, Xia, Tian, Xia, Weiliang, Xia, Yong, Xiao, Hengyi, Xiao, Jian, Xiao, Shi, Xiao, Wuhan, Xie, Chuan-Ming, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xiong, Yuyan, Xu, Chuanshan, Xu, Congfeng, Xu, Feng, Xu, Haoxing, Xu, Hongwei, Xu, Jian, Xu, Jianzhen, Xu, Jinxian, Xu, Liang, Xu, Xiaolei, Xu, Yangqing, Xu, Ye, Xu, Zhi-Xiang, Xu, Ziheng, Xue, Yu, Yamada, Takahiro, Yamamoto, Ai, Yamanaka, Koji, Yamashina, Shunhei, Yamashiro, Shigeko, Yan, Bing, Yan, Bo, Yan, Xianghua, Yan, Zhen, Yanagi, Yasuo, Yang, Dun-Sheng, Yang, Jin-Ming, Yang, Liu, Yang, Minghua, Yang, Pei-Ming, Yang, Peixin, Yang, Qian, Yang, Wannian, Yang, Wei Yuan, Yang, Xuesong, Yang, Yi, Yang, Ying, Yang, Zhifen, Yang, Zhihong, Yao, Meng-Chao, Yao, Pamela J, Yao, Xiaofeng, Yao, Zhenyu, Yao, Zhiyuan, Yasui, Linda S, Ye, Mingxiang, Yedvobnick, Barry, Yeganeh, Behzad, Yeh, Elizabeth S, Yeyati, Patricia L, Yi, Fan, Yi, Long, Yin, Xiao-Ming, Yip, Calvin K, Yoo, Yeong-Min, Yoo, Young Hyun, Yoon, Seung-Yong, Yoshida, Ken-Ichi, Yoshimori, Tamotsu, Young, Ken H, Yu, Huixin, Yu, Jane J, Yu, Jin-Tai, Yu, Jun, Yu, Li, Yu, W Haung, Yu, Xiao-Fang, Yu, Zhengping, Yuan, Junying, Yuan, Zhi-Min, Yue, Beatrice YJT, Yue, Jianbo, Yue, Zhenyu, Zacks, David N, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zaglia, Tania, Zakeri, Zahra, Zecchini, Vincent, Zeng, Jinsheng, Zeng, Min, Zeng, Qi, Zervos, Antonis S, Zhang, Donna D, Zhang, Fan, Zhang, Guo, Zhang, Guo-Chang, Zhang, Hao, Zhang, Hong, Zhang, Hong, Zhang, Hongbing, Zhang, Jian, Zhang, Jian, Zhang, Jiangwei, Zhang, Jianhua, Zhang, Jing-pu, Zhang, Li, Zhang, Lin, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xiangnan, Zhang, Xu Dong, Zhang, Yan, Zhang, Yang, Zhang, Yanjin, Zhang, Yingmei, Zhang, Yunjiao, Zhao, Mei, Zhao, Wei-Li, Zhao, Xiaonan, Zhao, Yan G, Zhao, Ying, Zhao, Yongchao, Zhao, Yu-xia, Zhao, Zhendong, Zhao, Zhizhuang J, Zheng, Dexian, Zheng, Xi-Long, Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Guang-Zhou, Zhou, Guofei, Zhou, Huiping, Zhou, Shu-Feng, Zhou, Xu-jie, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Wenhua, Zhu, Xiao-Feng, Zhu, Yuhua, Zhuang, Shi-Mei, Zhuang, Xiaohong, Ziparo, Elio, Zois, Christos E, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, and Zughaier, Susu M
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- 2016
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10. Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis
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Gogada, Raghu, Amadori, Michael, Zhang, Honghao, Jones, Anthony, Verone, Alissa, Pitarresi, Jason, Jandhyam, Sirisha, Prabhu, Varun, Black, Jennifer D., and Chandra, Dhyan
- Abstract
Previous studies have demonstrated that curcumin induces mitochondria-mediated apoptosis. However, understanding of the molecular mechanisms underlying curcumin-induced cell death remains limited. In this study, we demonstrate that curcumin treatment of cancer cells caused dose- and time-dependent caspase-3 activation, which is required for apoptosis as confirmed using the pan caspase inhibitor, z-VAD. Knockdown experiments and knockout cells excluded a role of caspase-8 in curcumin-induced caspase-3 activation. In contrast, Apaf-1 deficiency or silencing inhibited the activity of caspase-3, pointing to a requisite role of Apaf-1 in curcumin-induced apoptotic cell death. Curcumin treatment led to Apaf-1 upregulation both at the protein and mRNA levels. Cytochrome c release from mitochondria to the cytosol in curcumin-treated cells was associated with upregulation of proapoptotic proteins such as Bax, Bak, Bid, and Bim. Crosslinking experiments demonstrated Bax oligomerization during curcumin-induced apoptosis, suggesting that induced expression of Bax, Bid, and Bim causes Bax-channel formation on the mitochondrial membrane. The release of cytochrome c was unaltered in p53-deficient cells, whereas absence of p21 blocked cytochrome c release, caspase activation, and apoptosis. Importantly, p21-deficiency resulted in reduced expression of Apaf-1 during curcumin treatment, indicating a requirement of p21 in Apaf-1 dependent caspase activation and apoptosis. Together, our findings demonstrate that Apaf-1, Bax, and p21 as novel potential targets for curcumin or curcumin-based anticancer agents.
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- 2011
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11. NADPH oxidase 4 is an oncoprotein localized to mitochondria
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Graham, Kelly A., Kulawiec, Mariola, Owens, Kjerstin M., Li, Xiurong, Desouki, Mohamed M., Chandra, Dhyan, and Singh, Keshav K.
- Abstract
Reactive oxygen species (ROS) are known to be involved in many physiological and pathological processes. Initially ROS-producing NADPH oxidase (NOX) proteins were thought to be present in phagocytes. However, recent studies have demonstrated that NOX proteins are expressed in many other cell types and tissues. NOX family members' function seems to vary from tissue to tissue. We determined the expression of the NOX family of proteins (NOX1-5) in normal breast tissue and breast tumors. Our study revealed that normal breast tissues express NOX1, 4 and 5 genes. Similar pattern of expression was revealed in a breast epithelial cell line. We found that NOX4 was overexpressed in majority of breast cancer cell lines and primary breast tumors. NOX4 was also overexpressed in ovarian tumors. Overexpression of NOX4 in normal breast epithelial cells resulted in cellular senescence, resistance to apoptosis, and tumorigenic transformation. Overexpression of NOX4 in already transformed breast tumor cells also showed increased tumorigenicity. Strong evidence suggests that regulation of these processes occurs through NOX4 generation of ROS in the mitochondria. We demonstrate that the NOX4 protein contains a 73 amino acid long mitochondrial localization signal at the N-terminus that is capable of transporting a passenger protein GFP into the mitochondria. Treatment of NOX4 overexpressing cells with catalase resulted in decreased tumorigenic characteristics. Together, this study provides evidence for an oncogenic function for NOX4 protein localized to mitochondria and suggests that NOX4 is a source of ROS produced in the mitochondria. This study also identifies a possible treatment of NOX4-induced breast cancer by antioxidant treatment.
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- 2010
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12. Early Mitochondrial Activation and Cytochrome cUp-regulation during Apoptosis*210
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Chandra, Dhyan, Liu, Jun-Wei, and Tang, Dean G.
- Abstract
Apoptosis induced by many stimuli requires the mitochondrial respiratory chain (MRC) function. While studying the molecular mechanisms underlying this MRC-dependent apoptotic pathway, we find that apoptosis in multiple cell types induced by a variety of stimuli is preceded by an early induction of MRC proteins such as cytochrome c(which is encoded by a nuclear gene) and cytochrome coxidase subunit II (COX II) (which is encoded by the mitochondrial genome). Several non-MRC proteins localized in the mitochondria, e.g.Smac, Bim, Bak, and Bcl-2, are also rapidly up-regulated. The up-regulation of many of these proteins (e.g.cytochrome c, COX II, and Bim) results from transcriptional activation of the respective genes. The up-regulated cytosolic cytochrome crapidly translocates to the mitochondria, resulting in an accumulation of holocytochrome cin the mitochondria accompanied by increasing holocytochrome crelease into the cytosol. The increased cytochrome ctransport from cytosol to the mitochondria does not depend on the mitochondrial protein synthesis or MRC per se. In contrast, cytochrome crelease from the mitochondria involves dynamic changes in Bcl-2 family proteins (e.g.up-regulation of Bak, Bcl-2, and Bcl-xL), opening of permeability transition pore, and loss of mitochondrial membrane potential. Overexpression of cytochrome cenhances caspase activation and promotes cell death in response to apoptotic stimulation, but simple up-regulation of cytochrome cusing an ecdysone-inducible system is, by itself, insufficient to induce apoptosis. Taken together, these results suggest that apoptosis induced by many stimuli involves an early mitochondrial activation, which may be responsible for the subsequent disruption of MRC functions, loss of Δψm, cytochrome crelease, and ultimately cell death.
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- 2002
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13. Evidence That Arachidonate 15-Lipoxygenase 2 Is a Negative Cell Cycle Regulator in Normal Prostate Epithelial Cells*210
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Tang, Shaohua, Bhatia, Bobby, Maldonado, Carlos J., Yang, Peiying, Newman, Robert A., Liu, Junwei, Chandra, Dhyan, Traag, Jeanine, Klein, Russell D., Fischer, Susan M., Chopra, Dharam, Shen, Jianjun, Zhau, Haiyen E., Chung, Leland W.K., and Tang, Dean G.
- Abstract
15-Lipoxygenase 2 (15-LOX2) is a recently cloned human lipoxygenase that shows tissue-restricted expression in prostate, lung, skin, and cornea. The protein level and enzymatic activity of 15-LOX2 have been shown to be down-regulated in prostate cancers compared with normal and benign prostate tissues. The biological function of 15-LOX2 and the role of loss of 15-LOX2 expression in prostate tumorigenesis, however, remain unknown. We report the cloning and functional characterization of 15-LOX2 and its three splice variants (termed 15-LOX2sv-a, 15-LOX2sv-b, and 15-LOX2sv-c) from primary prostate epithelial cells. Western blotting with multiple primary prostate cell strains and prostate cancer cell lines reveals that the expression of 15-LOX2 is lost in all prostate cancer cell lines, accompanied by decreased enzymatic activity revealed by liquid chromatography/tandem mass spectrometry analyses. Further experiments show that the loss of 15-LOX2 expression results from transcriptional repression caused by mechanism(s) other than promoter hypermethylation or histone deacetylation. Subsequent functional studies indicate the following: 1) the 15-LOX2 product, 15(S)-hydroxyeicosatetraenoic acid, inhibits prostate cancer cell cycle progression; 2) 15-LOX2 expression in primary prostate epithelial cells is inversely correlated with cell cycle; and 3) restoration of 15-LOX2 expression in prostate cancer cells partially inhibits cell cycle progression. Taken together, these results suggest that 15-LOX2 could be a suppressor of prostate cancer development, which functions by restricting cell cycle progression.
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- 2002
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14. Radiation induced oxidative stress: II Studies in liver as a distant organ of tumor bearing mice
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Agrawal, Anjali, Chandra, Dhyan, and Kale, R.K.
- Abstract
Since the radiation dose tolerance of normal tissues/organs away from the site of tumor influences the success of radiation therapy of cancer, and antioxidant status is likely to be one of the factors to determine the tolerance; the radioresponse of antioxidant enzymes has been examined in the liver as a representative distant organ in the tumorbearing mice. Swiss albino male mice (7–8 weeks old) with Ehrlich solid tumor in the thigh pad were irradiated with different doses of γradiation (0–9 Gy) at a dose rate of 0.0153 Gy/s and the specific activities of enzymes involved in the free radical metabolism were determined in the liver. Except GST, the activities of SOD, DTD and Gly I as well as the GSH content were found to be higher in the liver of tumorbearing mice compared to the nontumor bearing mice. The catalase activity progressively decreased with dose in both the groups of mice. However, the activity was relatively higher in the liver of tumor bearing mice than the control. Thus, the radioresponse of antioxidant enzymes seemed to be significantly different in the liver of tumorburdened mice compared to controls. The enhanced activities might be due to relatively more damage caused by radiation. The higher levels of NO· and peroxidative damage in the liver of tumorbearing mice probably suggest this possibility. These findings of the present work might have some serious implications as the increased radiationdamage of the distant normal organs (due to tumor burden) is likely to adversely affect the therapeutic gain.
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- 2001
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15. Receptor-interacting Protein 140 Directly Recruits Histone Deacetylases for Gene Silencing*
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Wei, Li-Na, Hu, Xinli, Chandra, Dhyan, Seto, Edward, and Farooqui, Maria
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Receptor-interacting protein 140 (RIP140) encodes a histone deacetylase (HDAC) inhibitor-sensitive repressive activity. Direct interaction of RIP140 with HDAC1 and HDAC3 occurs in vitroand in vivoas demonstrated in co-immunoprecipitation and glutathione S-transferase pull-down experiments. The HDAC-interacting domain of RIP140 is mapped to its N-terminal domain, between amino acids 78 and 303 based upon glutathione S-transferase pull-down experiments. In chromatin immunoprecipitation assays, it is demonstrated that histone deacetylation occurs at the chromatin region of the Gal4 binding sites as a result of Gal4 DNA binding domain-tethered RIP expression. The immunocomplexes of RIP140 from cells transfected with RIP140 and HDAC are able to deacetylate histone proteins in vitro. This study presents the first evidence for RIP140 as a negative coregulator for nuclear receptor actions by directly recruiting histone deacetylases and categorizes RIP140 as a novel negative coregulator that is able to directly interact with HDACs.
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- 2000
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16. A Single-Organelle Optical Omics Platform for Cell Science and Biomarker Discovery
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Pliss, Artem, Kuzmin, Andrey N, Lita, Adrian, Kumar, Rahul, Celiku, Orieta, Atilla-Gokcumen, G. Ekin, Gokcumen, Omer, Chandra, Dhyan, Larion, Mioara, and Prasad, Paras N
- Abstract
Research in fundamental cell biology and pathology could be revolutionized by developing the capacity for quantitative molecular analysis of subcellular structures. To that end, we introduce the Ramanomics platform, based on confocal Raman microspectrometry coupled to a biomolecular component analysis algorithm, which together enable us to molecularly profile single organelles in a live-cell environment. This emerging omics approach categorizes the entire molecular makeup of a sample into about a dozen of general classes and subclasses of biomolecules and quantifies their amounts in submicrometer volumes. A major contribution of our study is an attempt to bridge Raman spectrometry with big-data analysis in order to identify complex patterns of biomolecules in a single cellular organelle and leverage discovery of disease biomarkers. Our data reveal significant variations in organellar composition between different cell lines. We also demonstrate the merits of Ramanomics for identifying diseased cells by using prostate cancer as an example. We report large-scale molecular transformations in the mitochondria, Golgi apparatus, and endoplasmic reticulum that accompany the development of prostate cancer. Based on these findings, we propose that Ramanomics datasets in distinct organelles constitute signatures of cellular metabolism in healthy and diseased states.
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- 2021
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