天然产物新靶点:自噬-溶酶体途径(英文)

The autophagy-lysosome pathway as the novel targets of natural products

Autophagy is an evolutionarily well conserved process in which the cellular components including damaged subcellular organelles are engulfed in autophagosome and eventually delivered to lysosome for degradation.It has been well studied that autophagy is closely implicated in many diseases such as cancer and neurodegenerative diseases.Therefore,the autophagy-lysosome pathway becomes an attractive target in developing novel therapeutic approaches.In the past several years,we have studied the effects of several natural products on the autophagy-lysosome pathway:(i)Andrographolide(Andro),a diterpenoid lactone isolated from an herbal plant Andrographispaniculata,is capable of suppressing autophagy and sensitizing cisplatin-mediated apoptosis in human cancer cells,via blockage of autophagosome-lysosome fusion;(ii)(-)-Epigallocatechin-3-gallate(EGCG),an important green tea polyphenol,induces lysosomal membrane permeabilization(LMP)and eventually leads to lysosome-associated cell death;and(iii)Artesunate(ART),an analog of artemisinin,an anti-malaria drug,is able to kill cancer cells via enhancing lysosomal function and induction of lysosomal degradation of ferritin.Collectively,our findings reveal novel insights into the molecular mechanisms underlying the anti-cancer properties of those natural compounds and demonstrate that targeting the autophagy-lysosome pathway could serve as a new strategy in developing anti-cancer therapeutic agents.