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.
Int J Cancer. 2011 Sep 1;129(5):1087-95. doi: 10.1002/ijc.25771. Epub 2011 Mar 25.
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.
半胱胺（CS）由于其出色的水溶性、低细胞毒性和良好的生物相容性，在许多生物医学和临床应用中都有应用。Brawer 等人的先前研究报告称，CS 处理的星形胶质细胞中出现了许多 Gomori 包涵体，这表明自噬的诱导。在这里，我们提供了一系列全面的证据，证明 CS 导致癌细胞中自噬体的积累。CS 对自噬过程产生了双相作用，在早期阶段增加自噬体的形成，而在后期阶段则阻止自噬降解。此外，我们表明 CS 增敏阿霉素诱导的 HeLa、B16 黑色素瘤和阿霉素耐药 MCF-7 细胞的化疗杀伤作用，并增强了阿霉素在小鼠黑色素瘤模型中的化疗疗效。最后，我们证明 CS 的化疗增敏作用至少部分依赖于其调节自噬的能力。我们的研究结果揭示了 CS 通过调节自噬增强阿霉素化疗效果的新生物学功能，并指出了 CS 在联合癌症化疗中的潜在用途。
