title: Anticancer potential of myricanone, a major bioactive component of Myrica cerifera: novel signaling cascade for accomplishing apoptosis.
abstract: Extract of Myrica cerifera bark has long been fruitfully used as a hepato-protective and anti-cancer drug in various complementary and alternative systems of medicine. Myricanone, its principal bioactive compound, had also been reported to have apoptosis-promoting ability. We evaluated its anti-cancer potential in vitro in HepG2 liver cancer cells and tried to understand the signal cascades involved in accomplishing apoptosis. Further, we ascertained by using a (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay (MTT) assay if it had cytotoxic effects on normal noncancerous liver cells (WRL-68). We deployed various tools and protocols, like phase contrast, scanning electron and fluorescence microscopies, performed an annexinV-FITC/PI assay and cell cycle analysis, and estimated the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization through flow cytometry. Further, analyses of cytochrome-c translocation and of HSP70 and caspase expressions were also done by using immunoblota and Enzyme linked immunosorbent assay (ELISA). Results revealed that myricanone induced apoptosis in HepG2 cells through generation of ROS, depolarization of the mitochondrial membrane, early release of cytochrome-c, down-regulation of HSP70 and activation of a caspase cascade; it had no, or insignificant, cytotoxic effects in WRL-68 cells in vitro and in mice in vivo. Thus, myricanone has great potential for use in formulating an effective drug against both hepatotoxicity and hepatocellular cancer.
authors: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani, India.
authors: Avijit
authors: A
authors: Paul
authors: Jayeeta
authors: J
authors: Das
authors: Sreemanti
authors: S
authors: Das
authors: Asmita
authors: A
authors: Samadder
authors: Anisur Rahman
authors: AR
authors: Khuda-Bukhsh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D031641:Myrica / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D036381:Diarylheptanoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C041795:myricanone; D045304:Cytochromes c
keywords: HSP70; HepG2 cells; apoptosis; cytochrome c; myricanone; reactive oxygen species