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The escalating rate of cancer cases, together with treatment deficiencies and long-term side effects of currently used cancer drugs, has made this disease a global burden of the 21st century. The number of breast and lung cancer patients has sharply increased worldwide in the last few years. Presently, surgical treatment, radiotherapy, chemotherapy, and immunotherapy strategies are used to cure cancer, which cause severe side effects, toxicities, and drug resistance. In recent years, anti-cancer peptides have become an eminent therapeutic strategy for cancer treatment due to their high specificity and fewer side effects and toxicity. This review presents an updated overview of different anti-cancer peptides, their mechanisms of action and current production strategies employed for their manufacture. In addition, approved and under clinical trials anti-cancer peptides and their applications have been discussed. This review provides updated information on therapeutic anti-cancer peptides that hold great promise for cancer treatment in the near future., QC 20230725

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

Background: Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an enzyme required for de novo purine biosynthesis, is associated with and involved in tumorigenesis. This study aimed to evaluate the role of PAICS in human breast cancer, which remains the most frequently diagnosed cancer and the leading cause of cancer-related death among women in less developed countries. Results: Lentivirus-based short hairpin RNA targeting PAICS specifically depleted its endogenous expression in ZR-75-30 and MDA-MB-231 breast cancer cells. Depletion of PAICS led to a significant decrease in cell viability and proliferation. To ascertain the mechanisms through which PAICS modulates cell proliferation, flow cytometry was performed, and it was confirmed that G1-S transition was blocked in ZR-75-30 cells through PAICS knockdown. This might have occurred partly through the suppression of Cyclin E and the upregulation of Cyclin D1, P21, and CDK4. Moreover, PAICS knockdown obviously promoted cell apoptosis in ZR-75-30 cells through the activation of PARP and caspase 3 and downregulation of Bcl-2 and Bcl-xl expression in ZR-75-30 cells. Conclusions: These findings demonstrate that PAICS plays an essential role in breast cancer proliferation in vitro, which provides a new opportunity for discovering and identifying novel effective treatment strategies.

Morphogenesis in multicellular organisms is accompanied by apoptotic cell behaviors: cell shrinkage and cell disappearance. The mechanical effects of these behaviors are spatiotemporally regulated within multicellular dynamics to achieve proper tissue sizes and shapes in three-dimensional (3D) space. To analyze 3D multicellular dynamics, 3D vertex models have been suggested, in which a reversible network reconnection (RNR) model has successfully expressed 3D cell rearrangements during large deformations. To analyze the effects of apoptotic cell behaviors on 3D multicellular morphogenesis, we modeled cell apoptosis based on the RNR model framework. Cell shrinkage was modeled by the potential energy as a function of individual cell times during the apoptotic phase. Cell disappearance was modeled by merging neighboring polyhedrons at their boundary surface according to the topological rules of the RNR model. To establish that the apoptotic cell behaviors could be expressed as modeled, we simulated morphogenesis driven by cell apoptosis in two types of tissue topology: 3D monolayer cell sheet and 3D compacted cell aggregate. In both types of tissue topology, the numerical simulations successfully illustrated that cell aggregates gradually shrank because of successive cell apoptosis. During tissue shrinkage, the number of cells in aggregates decreased while maintaining individual cell size and shape. Moreover, in case of localizing apoptotic cells within a part of the 3D monolayer cell aggregate, the cell apoptosis caused the global tissue bending by pulling on surrounding cells. In case of localizing apoptotic cells on the surface of the 3D compacted cell aggregate, the cell apoptosis caused successive, directional cell rearrangements from the inside to the surface. Thus, the proposed model successfully provided a basis for expressing apoptotic cell behaviors during 3D multicellular morphogenesis based on an RNR model framework.

Long noncoding RNAs (lncRNAs) are non-proten-coding transcripts of more than 200 nucleotides generated by RNA polymerase II and their expressions are tightly regulated in cell type specific- and/or cellular differential stage specific- manner. MIAT, originally isolated as a candidate gene for myocardial infarction, encodes lncRNA (termed MIAT). Here, we determined the expression level of MIAT in established leukemia/lymphoma cell lines and found its upregulation in lymphoid but not in myeloid cell lineage with mature B cell phenotype. MIAT expression level was further determined in chronic lymphocytic leukemias (CLL), characterized by expansion of leukemic cells with mature B phenotype, to demonstrate relatively high occurrence of MIAT upregulation in aggressive form of CLL carrying either 17p-deletion, 11q-deletion, or Trisomy 12 over indolent form carrying 13p-deletion. Furthermore, we show that MIAT constitutes a regulatory loop with OCT4 in malignant mature B cell, as was previously reported in mouse pulripotent stem cell, and that both molecules are essential for cell survival.

Long noncoding RNAs (lncRNAs) are non-proten-coding transcripts of more than 200 nucleotides generated by RNA polymerase II and their expressions are tightly regulated in cell type specific- and/or cellular differential stage specific- manner. MIAT, originally isolated as a candidate gene for myocardial infarction, encodes lncRNA (termed MIAT). Here, we determined the expression level of MIAT in established leukemia/lymphoma cell lines and found its upregulation in lymphoid but not in myeloid cell lineage with mature B cell phenotype. MIAT expression level was further determined in chronic lymphocytic leukemias (CLL), characterized by expansion of leukemic cells with mature B phenotype, to demonstrate relatively high occurrence of MIAT upregulation in aggressive form of CLL carrying either 17p-deletion, 11q-deletion, or Trisomy 12 over indolent form carrying 13p-deletion. Furthermore, we show that MIAT constitutes a regulatory loop with OCT4 in malignant mature B cell, as was previously reported in mouse pulripotent stem cell, and that both molecules are essential for cell survival.

The development of a series of fluorescent materials including heterocycle-functionalized luminogens with aggregation-induced/enhanced emission (AIE/AEE), long wavelength emission, and high solid state fluorescence quantum efficiency is contemplated. The described fluorescent materials are promising candidates in selective luminescence-based chemosensor for Hg2+ or ATP, fluorescent staining for mitochondria in living cells with high photostability, stimuli-responsive luminescent materials, and materials for optical waveguides. In addition, these heterocycle-functionalized luminogens are particularly useful as fluorescent labels for biopolymers such as peptides, antibodies, or nucleic acids, making them useful as AIE-active biocompatible probes for clinical cancer imaging and diagnostics.

The development of a series of fluorescent materials including heterocycle-functionalized luminogens with aggregation-induced/enhanced emission (AIE/AEE), long wavelength emission, and high solid state fluorescence quantum efficiency is contemplated. The described fluorescent materials are promising candidates in selective luminescence-based chemosensor for Hg2+ or ATP, fluorescent staining for mitochondria in living cells with high photostability, stimuli-responsive luminescent materials, and materials for optical waveguides. In addition, these heterocycle-functionalized luminogens are particularly useful as fluorescent labels for biopolymers such as peptides, antibodies, or nucleic acids, making them useful as AIE-active biocompatible probes for clinical cancer imaging and diagnostics.

The development of a series of fluorescent materials including heterocycle-functionalized luminogens with aggregation-induced/enhanced emission (AIE/AEE), long wavelength emission, and high solid state fluorescence quantum efficiency is contemplated. The described fluorescent materials are promising candidates in selective luminescence-based chemosensor for Hg2+ or ATP, fluorescent staining for mitochondria in living cells with high photostability, stimuli-responsive luminescent materials, and materials for optical waveguides. In addition, these heterocycle-functionalized luminogens are particularly useful as fluorescent labels for biopolymers such as peptides, antibodies, or nucleic acids, making them useful as AIE-active biocompatible probes for clinical cancer imaging and diagnostics.

In this paper we consider a two-phase model describing the growth of avascular solid tumors when taking into account the effects of cell-to-cell adhesion and taxis due to nutrient. The tumor is surrounded by healthy tissue which is the source of nutrient for tumor cells. In a three-dimensional context, we prove that the mathematical formulation corresponds to a well-posed problem, and find radially symmetric steady-state solutions of the problem. They appear in the regime where the rate of cell apoptosis to cell proliferation is less than the far field nutrient concentration. Furthermore, we study the stability properties of those radially symmetric equilibria and find, depending on the biophysical parameters involved in the problem, both stable and unstable regimes for tumor growth. Copyright © Cambridge University Press 2012.