The natural triterpene 3β,6β,16β-trihydroxy-lup-20(29)-ene obtained from the flowers of Combretum leprosum induces apoptosis in MCF-7 breast cancer cells

BMC Complementary and Alternative Medicine

Research Article

Dinara Jaqueline Moura¹  Cassiana Macagnan Viau²  Jenifer Saffi²  Valdir Alves Facundo³ 

[1] Department of Basic Health Sciences, Laboratory of Genetic Toxicology, UFCSPA, Porto Alegre, RS, Brazil;Department of Basic Health Sciences, Laboratory of Genetic Toxicology, UFCSPA, Porto Alegre, RS, Brazil;National Institute for Translational Research on Health and Environment in the Amazon Region - CNPq/INCT/INPeTAm, Rio de Janeiro, RJ, Brazil;Department of Medicine, Federal University of Rondônia - UNIR, Porto Velho, RO, Brazil;

关键词: Combretum leprosum;    3β;    6β;    16β-trihydroxy-lup-20(29)-ene triterpene;    Antiproliferative activity;    Cleaved caspase-9;    ROS;    Mitochondrial apoptotic pathway;   

DOI  :  10.1186/1472-6882-14-280

 received in 2014-03-25, accepted in 2014-07-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) is a pentacyclic triterpene obtained from the medicinal plant Combretum leprosum Mart. In folk medicine, this plant is popularly known as mofumbo, cipoaba or mufumbo, and is used to treat several diseases associated with inflammation and pain.MethodsWe investigated the antitumor efficacy of TTHL isolated from C. leprosum. The TTHL cytotoxic effect was investigated in MRC5, MCF-7, HepG2, T24, HCT116, HT29, and CACO-2 cells after 24, 48, 72 and 120 h of treatment. The mechanisms of cell death and DNA damage induction were investigated by flow cytometry and comet assay, respectively.ResultsThe results indicated that TTHL induced a time- and concentration-dependent growth inhibition in all human cancer cell lines. The cytotoxicity was more pronounced in MCF-7 breast cancer cells, with an IC50 of 0.30 μg/mL at 120 h. We therefore evaluated the cell death mechanism induced by TTHL (IC20, IC50, and IC80) in MCF-7 cells at 24 h. We found that the treatment with IC50 and IC80 TTHL for 24 h induced apoptosis in 14% (IC50) and 52% (IC80) of MCF-7 cells. The apoptosis induced by TTHL was accompanied by increased levels of both cleaved caspase-9 and intracellular ROS. In order to further understand the biological mechanism of TTHL-induced cytotoxicity, we have also investigated its effect on different Saccharomyces cerevisiae yeast strains. The mutant strains sod1 Δ, sod2 Δ, and sod1 Δsod2 Δ, which are deficient in superoxide dismutase antioxidant defenses, were hypersensitive to TTHL, suggesting that its capacity to disturb cellular redox balance plays a role in drug toxicity. Moreover, TTHL induced mutagenicity in the yeast strain XV185-14c.ConclusionsTaken together, the results suggest that TTHL forms covalent adducts with cellular macromolecules, potentially disrupting cellular function and triggering apoptosis.

【 授权许可】

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© Viau et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.