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1. Korean Red Ginseng Extract Increases Apoptosis by Activation of the Noxa Pathway in Colorectal Cancer

Author

Yoon A. Jeong, Bo Ram Kim, Dae Young Kim, Soyeon Jeong, Yoo Jin Na, Jung Lim Kim, Hye Kyeong Yun, Bu Gyeom Kim, Seong Hye Park, Min Jee Jo, Sun Il Lee, Byung-Cheol Han, Dae-Hee Lee, and Sang Cheul Oh

Subjects
endoplasmic reticulum stress, korean red ginseng, Noxa, reactive oxygen species, Nutrition. Foods and food supply, TX341-641
Abstract

Background: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. Methods: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. Results: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. Conclusion: Our results show that KRG can be used as a possible anticancer drug for patients with CRC

Published
2019
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2. Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells

Author

Jung Lim Kim, Seong Hye Park, Soyeon Jeong, Bo Ram Kim, Yoo Jin Na, Min Jee Jo, Yoon A Jeong, Hye Kyeong Yun, Dae Yeong Kim, Bu Gyeom Kim, SangGuan You, Sang Cheul Oh, and Dae-Hee Lee

Subjects
sea cucumber (SC), endoplasmic reticulum (ER) stress, X-linked inhibitor of apoptosis protein (XIAP), c-Jun N-terminal kinase (JNK), Nutrition. Foods and food supply, TX341-641
Abstract

Natural products have shown great promise in sensitizing cells to TNF-related apoptosis-inducing ligand (TRAIL) therapy. Sea cucumber (SC) extracts possess antitumor activity, and hence their potential to sensitize colorectal cancer (CRC) cells to TRAIL therapy was evaluated. This study used Western blotting to evaluate the combination effects of SC and TRAIL in CRC, and determined the molecular mechanism underlying these effects. SC fractions and TRAIL alone did not affect apoptosis; however, combined treatment dramatically induced the apoptosis of CRC cells, but not of normal colon cells. Combined treatment induced the expression of apoptotic proteins (poly (ADP-ribose) polymerase (PARP), caspase 3, and 8), and this effect was markedly inhibited by the ubiquitination of X-linked inhibitor of apoptosis protein (XIAP). SC did not affect the mRNA levels, but it increased proteasomal degradation and ubiquitination of the XIAP protein. Furthermore, SC induced reactive oxygen species (ROS) production, thereby activating c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress-related apoptotic pathways in CRC. Altogether, our results demonstrate that the SC F2 fraction may sensitize CRC cells to TRAIL-induced apoptosis through XIAP ubiquitination and ER stress.

Published
2019
Full Text
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3. Korean Red Ginseng Extract Increases Apoptosis by Activation of the Noxa Pathway in Colorectal Cancer

Author

Soyeon Jeong, Sang Cheul Oh, Yoo Jin Na, Dae Hee Lee, Bu Gyeom Kim, Sun Il Lee, Dae Young Kim, Yoon A. Jeong, Jung Lim Kim, Min Jee Jo, Byung Cheol Han, Hye Kyeong Yun, Seong Hye Park, and Bo Ram Kim

Subjects
0301 basic medicine, Programmed cell death, Colorectal cancer, korean red ginseng, Panax, Apoptosis, lcsh:TX341-641, Article, 03 medical and health sciences, Ginseng, 0302 clinical medicine, GINSENG EXTRACT, medicine, Humans, Viability assay, chemistry.chemical_classification, reactive oxygen species, Reactive oxygen species, Nutrition and Dietetics, Plant Extracts, Chemistry, Noxa, Endoplasmic reticulum, HCT116 Cells, medicine.disease, Antineoplastic Agents, Phytogenic, digestive system diseases, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Cancer research, endoplasmic reticulum stress, Colorectal Neoplasms, HT29 Cells, lcsh:Nutrition. Foods and food supply, Signal Transduction, Food Science
Abstract

Background: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. Methods: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. Results: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. Conclusion: Our results show that KRG can be used as a possible anticancer drug for patients with CRC

Published
2019
Full Text
View/download PDF

4. Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells

Author

Dae Hee Lee, Dae Yeong Kim, Min Jee Jo, Soyeon Jeong, Yoo Jin Na, Sang Cheul Oh, Bu Gyeom Kim, Bo Ram Kim, Jung Lim Kim, Yoon A. Jeong, Seong Hye Park, Sang Guan You, and Hye Kyeong Yun

Subjects
0301 basic medicine, Colon, Poly ADP ribose polymerase, Sea Cucumbers, endoplasmic reticulum (ER) stress, lcsh:TX341-641, Caspase 3, Antineoplastic Agents, Apoptosis, X-Linked Inhibitor of Apoptosis Protein, Inhibitor of apoptosis, Article, TNF-Related Apoptosis-Inducing Ligand, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, Animals, Humans, X-linked inhibitor of apoptosis protein (XIAP), chemistry.chemical_classification, Reactive oxygen species, Biological Products, Caspase 8, Nutrition and Dietetics, Kinase, Tumor Necrosis Factor-alpha, c-Jun N-terminal kinase (JNK), JNK Mitogen-Activated Protein Kinases, Ubiquitination, Drug Synergism, Endoplasmic Reticulum Stress, XIAP, Receptors, TNF-Related Apoptosis-Inducing Ligand, 030104 developmental biology, chemistry, Stichopus, 030220 oncology & carcinogenesis, Cancer research, Unfolded protein response, Poly(ADP-ribose) Polymerases, Colorectal Neoplasms, Reactive Oxygen Species, lcsh:Nutrition. Foods and food supply, sea cucumber (SC), Food Science
Abstract

Natural products have shown great promise in sensitizing cells to TNF-related apoptosis-inducing ligand (TRAIL) therapy. Sea cucumber (SC) extracts possess antitumor activity, and hence their potential to sensitize colorectal cancer (CRC) cells to TRAIL therapy was evaluated. This study used Western blotting to evaluate the combination effects of SC and TRAIL in CRC, and determined the molecular mechanism underlying these effects. SC fractions and TRAIL alone did not affect apoptosis, however, combined treatment dramatically induced the apoptosis of CRC cells, but not of normal colon cells. Combined treatment induced the expression of apoptotic proteins (poly (ADP-ribose) polymerase (PARP), caspase 3, and 8), and this effect was markedly inhibited by the ubiquitination of X-linked inhibitor of apoptosis protein (XIAP). SC did not affect the mRNA levels, but it increased proteasomal degradation and ubiquitination of the XIAP protein. Furthermore, SC induced reactive oxygen species (ROS) production, thereby activating c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress-related apoptotic pathways in CRC. Altogether, our results demonstrate that the SC F2 fraction may sensitize CRC cells to TRAIL-induced apoptosis through XIAP ubiquitination and ER stress.

Published
2019

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