Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways.

Leong, K.H. (2013) Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways. BMC Complementary and Alternative Medicine, 13. pp. 166-173. DOI https://doi.org/10.1186/1472-6882-13-166.

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Abstract

Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called “Kayakalp”, commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.The MTT assay showed that CACF dose-dependently inhibited cell growth of A375, while exerted less cytotoxic effect on normal primary epithelial melanocytes. We demonstrated that CACF induced cell growth inhibition through apoptosis, as evidenced by cell shrinkage, increased annexin V staining and formation of membrane blebs. CACF treatment also resulted in higher reactive oxygen species (ROS) production and lower Bcl-2 expression, leading to decrease mitochondrial membrane potential (MMP). Disruption of the MMP facilitated the release of mitochondrial cytochrome c, which activates caspase-9 and downstream caspase-3/7, resulting in DNA fragmentation and up-regulation of p53 in melanoma cells. Moreover, CACF prevented TNF-α-induced NF-κB nuclear translocation, which further committed A375 cells toward apoptosis.

Item Type: Article
Funders: UM High Impact Research Grant (HIR: E00002-20001), BKP Grant (BK011-2012), UM Research Grant (RP001-2012B)
Uncontrolled Keywords: Centratherum anthelminticum, Melanoma, Caspase cascade, Apoptosis, Bcl-2, p53, NF-κB
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Q Science > QK Botany
R Medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
R Medicine > RV Botanic, Thomsonian, and eclectic medicine
Divisions: Faculty of Medicine
Depositing User: Dr. Leong Kok Hoong
Date Deposited: 22 May 2014 02:15
Last Modified: 31 Jul 2018 04:25
URI: http://eprints.um.edu.my/id/eprint/10003

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