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Autophagy‐mediated chemosensitization by cysteamine in cancer cells
Author(s) -
Wan XiaoMei,
Zheng Fang,
Zhang Li,
Miao YanYan,
Man Na,
Wen LongPing
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25771
Subject(s) - autophagy , doxorubicin , cysteamine , hela , cytotoxicity , melanoma , cancer cell , cancer research , pharmacology , chemotherapy , chemistry , cell culture , medicine , biology , in vitro , cancer , biochemistry , apoptosis , genetics
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.