title: Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells.
abstract: Resistance of cancer cells to chemotherapy is a significant problem in oncology, and the development of sensitising agents or small-molecules with new mechanisms of action to kill these cells is needed. Autophagy is a cellular process responsible for the turnover of misfolded proteins or damaged organelles, and it also recycles nutrients to maintain energy levels for cell survival. In some apoptosis-resistant cancer cells, autophagy can also enhance the efficacy of anti-cancer drugs through autophagy-mediated mechanisms of cell death. Because the modulation of autophagic processes can be therapeutically useful to circumvent chemoresistance and enhance the effects of cancer treatment, the identification of novel autophagic enhancers for use in oncology is highly desirable. Many novel anti-cancer compounds have been isolated from natural products; therefore, we worked to discover natural, anti-cancer small-molecule enhancers of autophagy. Here, we have identified a group of natural alkaloid small-molecules that function as novel autophagic enhancers. These alkaloids, including liensinine, isoliensinine, dauricine and cepharanthine, stimulated AMPK-mTOR dependent induction of autophagy and autophagic cell death in a panel of apoptosis-resistant cells. Taken together, our work provides novel insights into the biological functions, mechanisms and potential therapeutic values of alkaloids for the induction of autophagy.
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Betty Yuen Kwan
authors: BY
authors: Law
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Wai Kit
authors: WK
authors: Chan
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Su Wei
authors: SW
authors: Xu
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Jing Rong
authors: JR
authors: Wang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Li Ping
authors: LP
authors: Bai
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Liang
authors: L
authors: Liu
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors: Vincent Kam Wai
authors: VK
authors: Wong
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight
chemical_list: D000470:Alkaloids