Autophagy-mediated chemosensitization by cysteamine in cancer cells
Xiao-Mei Wan
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
Search for more papers by this authorFang Zheng
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
Search for more papers by this authorLi Zhang
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
Search for more papers by this authorYan-Yan Miao
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
Search for more papers by this authorCorresponding Author
Na Man
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
Tel.: +86-551-3600051, Fax: +86-551-3600051
Na Man, 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
Long-Ping Wen, 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
Search for more papers by this authorCorresponding Author
Long-Ping Wen
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
Tel.: +86-551-3600051, Fax: +86-551-3600051
Na Man, 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
Long-Ping Wen, 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
Search for more papers by this authorXiao-Mei Wan
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
Search for more papers by this authorFang Zheng
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
Search for more papers by this authorLi Zhang
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
Search for more papers by this authorYan-Yan Miao
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
Search for more papers by this authorCorresponding Author
Na Man
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
Tel.: +86-551-3600051, Fax: +86-551-3600051
Na Man, 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
Long-Ping Wen, 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
Search for more papers by this authorCorresponding Author
Long-Ping Wen
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
Tel.: +86-551-3600051, Fax: +86-551-3600051
Na Man, 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
Long-Ping Wen, 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
Search for more papers by this authorAbstract
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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