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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.

Viau CM, Moura DJ, Facundo VA, Saffi J - BMC Complement Altern Med (2014)

Bottom Line: 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.In order to further understand the biological mechanism of TTHL-induced cytotoxicity, we have also investigated its effect on different Saccharomyces cerevisiae yeast strains.Taken together, the results suggest that TTHL forms covalent adducts with cellular macromolecules, potentially disrupting cellular function and triggering apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Health Sciences, Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil. jenifers@ufcspa.edu.br.

ABSTRACT

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.

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Related in: MedlinePlus

Chemical structure of TTHL (3β,6β,16β-trihydroxy-lup-20(29)-ene) isolated product fromCombretum leprosum.
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Fig1: Chemical structure of TTHL (3β,6β,16β-trihydroxy-lup-20(29)-ene) isolated product fromCombretum leprosum.

Mentions: In North and Northeastern Brazil, the species Combretum leprosum Mart. is popularly known as mofumbo, cipoaba or mufumbo. Infusions prepared with the aerial parts (stems, leaves and flowers) and roots of C. leprosum are used in folk medicine to heal wounds, to treat hemorrhages, or as a sedative[9, 10]. According to phytochemical analysis, C. leprosum is rich in compounds such as cycloartanes, triterpenes [arjunolic, mollic acid and 3β,6β,16β-trihydroxy-lup-20(29)-ene (TTHL - Figure 1)], and flavonoids (3-O-methylquercetin, 5,3′-dihydroxy-3,7,4′-trimethoxyflavone, 5,3′,4′-trihydroxy-3,7-dimethoxyflavone, and quercetin), and some of these substances have proven biological activity[9, 11–15].Figure 1


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.

Viau CM, Moura DJ, Facundo VA, Saffi J - BMC Complement Altern Med (2014)

Chemical structure of TTHL (3β,6β,16β-trihydroxy-lup-20(29)-ene) isolated product fromCombretum leprosum.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4129108&req=5

Fig1: Chemical structure of TTHL (3β,6β,16β-trihydroxy-lup-20(29)-ene) isolated product fromCombretum leprosum.
Mentions: In North and Northeastern Brazil, the species Combretum leprosum Mart. is popularly known as mofumbo, cipoaba or mufumbo. Infusions prepared with the aerial parts (stems, leaves and flowers) and roots of C. leprosum are used in folk medicine to heal wounds, to treat hemorrhages, or as a sedative[9, 10]. According to phytochemical analysis, C. leprosum is rich in compounds such as cycloartanes, triterpenes [arjunolic, mollic acid and 3β,6β,16β-trihydroxy-lup-20(29)-ene (TTHL - Figure 1)], and flavonoids (3-O-methylquercetin, 5,3′-dihydroxy-3,7,4′-trimethoxyflavone, 5,3′,4′-trihydroxy-3,7-dimethoxyflavone, and quercetin), and some of these substances have proven biological activity[9, 11–15].Figure 1

Bottom Line: 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.In order to further understand the biological mechanism of TTHL-induced cytotoxicity, we have also investigated its effect on different Saccharomyces cerevisiae yeast strains.Taken together, the results suggest that TTHL forms covalent adducts with cellular macromolecules, potentially disrupting cellular function and triggering apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Health Sciences, Laboratory of Genetic Toxicology - UFCSPA, Porto Alegre, RS, Brazil. jenifers@ufcspa.edu.br.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus