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

Jenifer Saffi³  Valdir Alves Facundo¹  Dinara Jaqueline Moura²  Cassiana Macagnan Viau³ 

[1] Department of Medicine, Federal University of Rondônia - UNIR, Porto Velho, RO, 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

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

Others  :  1087104
DOI  :  10.1186/1472-6882-14-280

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

【 摘 要 】

Background

The 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.

Methods

We 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.

Results

The 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 sod1Δ, sod2Δ, and sod1Δsod2Δ, 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.

Conclusions

Taken together, the results suggest that TTHL forms covalent adducts with cellular macromolecules, potentially disrupting cellular function and triggering apoptosis.

【 授权许可】

   
2014 Viau et al.; licensee BioMed Central Ltd.

【 图 表 】

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