title: Autophagy-mediated chemosensitization by cysteamine in cancer cells.
abstract: Cysteamine (CS) has many biomedical and clinical applications because of its excellent water solubility, low cytotoxicity and good biocompatibility. A previous study by Brawer et al. reported the occurrence of many Gomori inclusion bodies in CS-treated astrocytes, which would suggest the induction of autophagy. Here we provided a comprehensive line of evidence demonstrating that CS caused autophagosome accumulation in cancer cells. CS exerted a biphasic effect on the autophagy process, increasing the formation of autophagosomes in the early phase and blocking the autophagic degradation in a later phase. Furthermore, we showed that CS sensitized doxorubicin-elicited chemotherapeutic killing in HeLa, B16 melanoma and doxorubicin-resistant MCF-7 cells and also enhanced chemotherapeutic efficacy of doxorubicin in a mouse melanoma model. Finally, we demonstrated that the chemosensitizing effect of CS was at least partly dependent on its ability to modulate autophagy. Our results revealed a novel biological function for CS in enhancing the chemotherapeutic effect of doxorubicin through autophagy modulation and pointed to the potential use of CS in adjunct cancer chemotherapy.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Wan
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Miao
authors.forename: Na
authors.initials: N
authors.lastname: Man
authors.forename: Long-Ping
authors.initials: LP
authors.lastname: Wen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001343:Autophagy; D003543:Cysteamine / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D003543:Cysteamine; D004317:Doxorubicin