Abyssinone V-4′ Methyl Ether, a Flavanone Isolated from Erythrina droogmansiana, Exhibits Cytotoxic Effects on Human Breast Cancer Cells by Induction of Apoptosis and Suppression of Invasion

Abyssinone V-4′ methyl ether (AVME) isolated from Erythrina droogmansiana was recently reported to exhibit anti-mammary tumor effect in mice. The present work was therefore aimed at elucidating its cellular and molecular mechanisms. To achieve our goal, the cytotoxicity of AVME against tumoral and non-tumoral cell lines was evaluated by resazurin reduction test; flow cytometry allowed us to evaluate the cell cycle and mechanisms of cell death; the mitochondrial transmembrane potential, reactive oxygen species (ROS) levels, and caspase activities as well as apoptosis-regulatory proteins (Bcl-2 and Bcl-XL) were measured in MDA-MB-231 cells. Further, the antimetastatic potential of AVME was evaluated by invasion assay. AVME exhibited cytotoxic effects in all tested tumor cell lines and induced a significant increase in the percentage of MDA-MB-231 cells at G2/M and S phases of the cell cycle in a concentration-dependent manner. AVME also induced apoptosis in MDA-MB-231 cells, which was accompanied by the activation of caspase-3 and caspase-9 and downregulation of Bcl-2 and Bcl-XL proteins. Moreover, AVME suppressed cancer cell invasion by the inhibition of the metalloproteinase-9 activity. Findings from this study suggest that AVME has anti-breast cancer activities expressed through mitochondrial proapoptotic pathway including impairment of aggressive behaviors of breast cancer cells

Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study

Abstract Background Ficus umbellata is a medicinal plant previously shown to endow estrogenic properties. Its major component was isolated and characterized as 7-methoxycoumarin (MC). Noteworthy, coumarins and the respective active metabolite 7-hydroxycoumarin analogs have shown aromatase inhibitory activity, which is of particular interest in the treatment of estrogen-dependent cancers. The present work aimed at evaluating the estrogenic/antiestrogenic effects of MC in vitro and in vivo. Methods To do so, in vitro assays using E-screen and reporter gene were done. In vivo, a 3-day uterotrophic assay followed by a postmenopausal-like rat model to characterize MC as well as F. umbellata aqueous extract in ovariectomized Wistar rats was performed. The investigations focused on histological (vaginal and uterine epithelial height) and morphological (uterine wet weight, vagina stratification and cornification) endpoints, bone mass, biochemical parameters and lipid profile. Results MC induced a significant (p < 0.05) MCF-7 cell proliferation at a concentration of 0.1 μM, but did not inhibit the effect induced by estradiol in both E-screen and reporter gene assays. In vivo, MC treatment did not show an uterotrophic effect in both rat models used. However, MC (1 mg/kg) induced a significant increase (p < 0.01) of vaginal epithelial height. No significant change was observed with MC in abdominal fat weight, serum lipid levels and bone weight. Conclusion These results suggest that MC has a weak estrogenic activity in vitro and in vivo that accounts only in part to the estrogenicity of the whole plant extract. MC could be beneficial with regard to vagina dryness as it showed a tissue specific effect without exposing the uterus to a potential tumorigenic growth

Additional file 1: Table S1. of Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study

Summary of compounds separated and identified in F. umbellata aqueous extract by UHPLC-ESI-HRMS analysis in the negative ion mode. Figure S1. Microphotographs of HE-stained sections (400×) of liver, lungs, kidneys and femur from different experimental rat groups in postmenopausal-like condition after 3 weeks of treatment. SHAM = Sham operated rats treated with vehicle as normal control; OVX = Ovariectomized rats treated with vehicle as negative control; E2V = Ovariectomized rats treated with estradiol valerate at the dose of dose 1 mg/kg BW as positive control; FU 50 and 200 = Ovariectomized rats treated with F. umbellata aqueous extract at the doses of 50 and 200 mg/kg BW, respectively; MC = Ovariectomized rats treated with 7-methoxycoumarin at the dose of 1 mg/kg BW. Vp = portal veine, H = Hepatocyte; S = sinusoids; A = alveol; Ba = Aveolar bag; TB = Trabecular bone; MB = marrow bone; Mi = microglie; Ne = Neurone; Co = Cortex. G = Glomerula; Dt = Distal tube; Pt = Proximal tube. (DOCX 797 kb

Additional file 1: of Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms

Figure S1. 1H NMR (600 MHz, CD3OD) spectrum of compound 6. Figure S2. ESI-MS (negative mode ionization) spectrum of compound 6. Figure S3. 1H NMR (600 MHz, CD3OD) spectrum of compound 13. Figure S4. ESI-MS (positive mode ionization) spectrum of compound 13. (DOC 112 kb