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| Format: | Artículo científico |
| Language: | en |
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Archivum immunologiae et therapiae experimentalis
2026
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41420872/ |
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| author | Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih |
| author_facet | Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih |
| collection | PubMed - marine biology |
| contents | Diphenyl Disulfide Exerts Dual Cytotoxic Effects by Inducing Ferroptosis and Apoptosis in Melanoma Cells. Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih Ferroptosis Humans Melanoma Apoptosis Cell Line, Tumor Antineoplastic Agents Signal Transduction Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Lipid Peroxidation NF-E2-Related Factor 2 Skin Neoplasms Autophagy Cell Survival Disulfides Phosphatidylinositol 3-Kinases Phospholipid Hydroperoxide Glutathione Peroxidase Amino Acid Transport System y+ Melanoma is a highly aggressive and heterogeneous form of skin cancer with limited effective treatment options. Although substantial progress has been made in immunotherapy, chemotherapy still serves as an essential alternative therapeutic strategy for many patients. Diphenyl disulfide (DPDS), a small molecule composed of two phenyl groups linked by a disulfide bond, has been reported to exert antioxidant and anticancer activities across several types of malignancies. In this study, we examined the cytotoxic effects of DPDS on melanoma cells and investigated the underlying mechanisms responsible for its antitumor activity. Our results showed that DPDS induces both ferroptosis and apoptosis in melanoma cells in a time-dependent manner. At 24 h, DPDS promoted lipid peroxidation, enhanced xCT ubiquitination, and reduced GPX4 expression, all of which are characteristic hallmarks of ferroptosis. Whereas at 48 h, apoptosis occurred, likely because of NRF2 phosphorylation inhibition, which initially protected against cell death. Additionally, DPDS inhibited the PI3K/AKT/mTOR pathway, leading to decreased mTOR expression and increased autophagy levels. Furthermore, the inhibition of ferroptosis or autophagy partially restored cell viability, suggesting a complex interplay between these pathways in DPDS-induced cytotoxicity. These findings highlight that DPDS may be a potential therapeutic agent for melanoma that functions by leveraging dual programmed cell death mechanisms and targeting the PI3K/AKT/mTOR signaling pathway. |
| format | Artículo científico |
| id | pubmed_41420872 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Archivum immunologiae et therapiae experimentalis |
| record_format | pubmed |
| spellingShingle | Diphenyl Disulfide Exerts Dual Cytotoxic Effects by Inducing Ferroptosis and Apoptosis in Melanoma Cells. Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih Ferroptosis Humans Melanoma Apoptosis Cell Line, Tumor Antineoplastic Agents Signal Transduction Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Lipid Peroxidation NF-E2-Related Factor 2 Skin Neoplasms Autophagy Cell Survival Disulfides Phosphatidylinositol 3-Kinases Phospholipid Hydroperoxide Glutathione Peroxidase Amino Acid Transport System y+ Diphenyl Disulfide Exerts Dual Cytotoxic Effects by Inducing Ferroptosis and Apoptosis in Melanoma Cells. Chen, Sheng-Yuan Shu, En-De Huang, Jiann-Jyh Chen, Yen-Chun Hsu, Sheng-Kai Chang, Wen-Tsan Lin, I-Ling Kuo, Chia-Hung Tsai, Ming-Fong Wen, Zhi-Hong Chiu, Chien-Chih Ferroptosis Humans Melanoma Apoptosis Cell Line, Tumor Antineoplastic Agents Signal Transduction Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Lipid Peroxidation NF-E2-Related Factor 2 Skin Neoplasms Autophagy Cell Survival Disulfides Phosphatidylinositol 3-Kinases Phospholipid Hydroperoxide Glutathione Peroxidase Amino Acid Transport System y+ Melanoma is a highly aggressive and heterogeneous form of skin cancer with limited effective treatment options. Although substantial progress has been made in immunotherapy, chemotherapy still serves as an essential alternative therapeutic strategy for many patients. Diphenyl disulfide (DPDS), a small molecule composed of two phenyl groups linked by a disulfide bond, has been reported to exert antioxidant and anticancer activities across several types of malignancies. In this study, we examined the cytotoxic effects of DPDS on melanoma cells and investigated the underlying mechanisms responsible for its antitumor activity. Our results showed that DPDS induces both ferroptosis and apoptosis in melanoma cells in a time-dependent manner. At 24 h, DPDS promoted lipid peroxidation, enhanced xCT ubiquitination, and reduced GPX4 expression, all of which are characteristic hallmarks of ferroptosis. Whereas at 48 h, apoptosis occurred, likely because of NRF2 phosphorylation inhibition, which initially protected against cell death. Additionally, DPDS inhibited the PI3K/AKT/mTOR pathway, leading to decreased mTOR expression and increased autophagy levels. Furthermore, the inhibition of ferroptosis or autophagy partially restored cell viability, suggesting a complex interplay between these pathways in DPDS-induced cytotoxicity. These findings highlight that DPDS may be a potential therapeutic agent for melanoma that functions by leveraging dual programmed cell death mechanisms and targeting the PI3K/AKT/mTOR signaling pathway. |
| title | Diphenyl Disulfide Exerts Dual Cytotoxic Effects by Inducing Ferroptosis and Apoptosis in Melanoma Cells. |
| topic | Ferroptosis Humans Melanoma Apoptosis Cell Line, Tumor Antineoplastic Agents Signal Transduction Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Lipid Peroxidation NF-E2-Related Factor 2 Skin Neoplasms Autophagy Cell Survival Disulfides Phosphatidylinositol 3-Kinases Phospholipid Hydroperoxide Glutathione Peroxidase Amino Acid Transport System y+ |
| url | https://pubmed.ncbi.nlm.nih.gov/41420872/ |