Isolation of a New Sesquiterpene Lactone From Vernonia Zeylanica (L) Less and its Anti-Proliferative Effects in Breast Cancer Cell Lines

Author(s): Anuka S. Mendis* , Ira Thabrew , Meran K. Ediriweera , Sameera R. Samarakoon , Kamani H. Tennekoon , Achyut Adhikari* , Egodage D. de Silva .

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 3 , 2019

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Abstract:

Background/Objective: Vernonia zeylanica (L) less is an endemic plant to Sri Lanka. The present study was designed to isolate potential cytotoxic compound/s from chloroform and ethyl acetate extracts of V. zeylanica by bio-activity guided isolation and to evaluate its anti-proliferative effects in three breast cancer phenotypes (MCF -7, MDA-MB-231, SKBR-3).

Methods: Combined chloroform and ethyl acetate extracts were subjected to chromatographic separations to isolate a compound (1) and the structure of the isolated compound was elucidated using 1H, 13C and mass spectroscopic techniques. Cytotoxic effects of the compound were evaluated by the sulforhodamine B (SRB) and the MTT (3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Effects of the compound on apoptosis were evaluated by fluorescent microscopy, caspase 3/7 activation, DNA fragmentation and real time PCR. Effects of the compound on the expression of heat shock protein complex were also evaluated by real time PCR and immunofluorescence.

Results: Isolated compound was identified as a new sesquiterpene lactone (vernolactone). The compound mediated significant cytotoxic effects in SKBR-3 and MDA-MB-231 breast cancer cells, with little effect in MCF-7 and normal mammary epithelial MCF-10A cells. Morphological changes, DNA fragmentation, increased caspase 3/7 activities and up-regulation of p53, Bax and down regulation of Survivin confirmed the proapoptotic effects of the compound. Significant inhibition of HSP complex related genes were also observed in SKBR-3 and MDA-MB-231 breast cancer cells.

Conclusion: Overall results indicate that vernolactone can mediate its cytotoxic effects via apoptosis and modulating the HSP complex.

Keywords: Vernonia zeylanica (L) less, vernolactone, breast cancer, phenotype cells, heat shock proteins, apoptosis.

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VOLUME: 19
ISSUE: 3
Year: 2019
Page: [410 - 424]
Pages: 15
DOI: 10.2174/1871520619666181128163359
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