Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 129, Issue 5, Pages 1087-1095Publisher
WILEY
DOI: 10.1002/ijc.25771
Keywords
cysteamine; chemosensitization; autophagy; chemotherapy; doxorubicin
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Funding
- Chinese Ministry of Sciences [2006CB933300, 2007CB935800]
- Natural Science Foundation of China [30721002, 31071211, 30830036]
- Chinese Academy of Sciences [KSCX2-YW-R-139]
- Scientific and Technological Major Special Project [2009ZX09103-650]
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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.
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