𝔖 Bobbio Scriptorium
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Autophagy-mediated chemosensitization by cysteamine in cancer cells

✍ Scribed by Xiao-Mei Wan; Fang Zheng; Li Zhang; Yan-Yan Miao; Na Man; Long-Ping Wen


Publisher
John Wiley and Sons
Year
2011
Tongue
French
Weight
497 KB
Volume
129
Category
Article
ISSN
0020-7136

No coin nor oath required. For personal study only.

✦ Synopsis


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.


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