Graveoline isolated from ethanolic extract of Ruta graveolens triggers apoptosis and autophagy in skin melanoma cells: a novel apoptosis-independent autophagic signaling pathway

Phytotherapy Research : PTR
Samrat GhoshAnisur Rahman Khuda-Bukhsh

Abstract

Anti-cancer drugs generally kill cancer cells by apoptosis but fail to do so when they become resistant and escape apoptosis signals. But these resistant cells can still be killed by autophagy. Therefore, drugs having both apoptotic and autophagic abilities are solicited in effective cancer management. In search of such a drug, we examined the efficacy of graveoline, a bioactive compound isolated from Ruta graveolens on skin melanoma A375 cells through the use of specific signaling cascades and their inhibitors. Cytotoxicity of graveoline was tested by conducting MTT assay. Induction of autophagy and apoptosis was checked. Expression of related proteins and their localization were studied by conducting immunoblot assay and through confocal microscopy, respectively. We found graveoline-induced Beclin-1 associated autophagy in A375 cells and 3-methyladenine, an inhibitor of autophagy did not affect apoptosis. Conversely, caspase inhibitor that blocked apoptosis did not affect autophagic cell death, suggesting thereby that these two were independent events. Use of reactive oxygen species (ROS) scavengers inhibited cell death, but blocking autophagy did not affect graveoline-induced ROS generation, suggesting that ROS generation en...Continue Reading

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Citations

Jan 26, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zeng LiJuan Jin
Oct 30, 2016·Biochemical Pharmacology·Heather Graham Hambright, Rita Ghosh
May 5, 2020·Current Drug Targets·Fatemeh Forouzanfar, Seyed Hadi Mousavi
Jun 14, 2020·Journal of Ethnopharmacology·Alexandra T CoimbraAna Paula Duarte
Jul 10, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Menglin LiuYanfei Li

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