Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats.

BACKGROUND: Numerous studies have reported the anti-cancer effects of different parts of Annona muricata Linn, however ; most of them focused on the in vitro evaluation of isolates. In vivo evidence on which part is best suited for breast cancer chemoprevention remains to be demonstrated. This is a comparative study of the effects of A. muricata fruit and leaves extracts on DMBA induced-breast cancer in rats. METHODS: Rats exposed to DMBA (50 mg/kg, s.c.), were treated with A. muricata fruit aqueous extract at 200 mg/kg BW (3 days/week or daily) and A. muricata Linn leaves ethanolic extract at 200 mg/kg daily. Positive control group received tamoxifen at 3.3 mg/kg, while the normal and diseased controls received vehicle. After 20 weeks of treatment, the tumor incidence, tumor burden, tumor volume, histopathology, protein and CA 15 - 3 levels as well as antioxidant status, pro-inflammatory cytokines were assessed. RESULTS: Thus, 100% of diseased rats presented cribriform ductal carcinoma of SBR grade III. A. muricata extracts (leaves and fruit) and tamoxifen significantly reduced death and tumor incidences, volume and weight of the tumors, total protein and CA15-3 levels compared to the DMBA group. They exhibited antioxidant activity, through an increase in the GSH level and SOD and catalase activities with reduced levels of MDA compared to DMBA group. TNF-α, IL-6 and INF-γ levels reduced with regards to A. muricata treatment. CONCLUSION: These results confirm the anti-breast cancer effect of A. muricata, however, the aqueous fruit extract was more potent than the ethanolic leaves extract.

Effects of Hibiscus sabdariffa Calyxes Aqueous Extract on Antioxidant Status and Histopathology in Mammary Tumor-Induced in Rats.

Breast cancer is a major threat worldwide. Hibiscus sabdariffa is widely consumed as beverage in sub-Saharan Africa for its anticancer potential. The present study therefore aimed at scientifically verifying its anticancer effect in rats. For this, 48 Wistar rats (∼55 days) were treated either with tamoxifen at 3.3 mg/kg BW (standard) or with a decoction of H. sabdariffa (125, 250, and 500 mg/kg BW) or distilled water (vehicle). Breast cancer was induced by a single dose of 50 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA). At the end of the 21 weeks of treatment, the tumor incidence, tumor morphology, histopathology, as well as some biochemical parameters in the tumors were assessed. As a result, 86% of DMBA's rats developed mammary tumors. The H. sabdariffa extract (125 and 250 mg/kg) reduced tumor incidence by 63% and 75%, respectively; inhibited tumor burden by 84.86% and 38.78%, respectively, and decreased tumor volume by more than 72% compared to the DMBA group. It also protected rats against DMBA-induced diffuse breast neoplasia, and the optimal effect was recorded at 125 mg/kg. Furthermore, it significantly increases the SOD activity and decreases the MDA level. In summary, H. sabdariffa has antibreast tumor and antioxidant properties in rats, which could justify its common use to treat cancer.

Anti-breast cancer potential of Anonidium mannii (Oliv.) Engl. & Diels barks ethanolic extract: UPLC-ESI-QTOF-MS detection of anticancer alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.

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.

Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo.

Background Phytoestrogens are natural compounds known as natural selective estrogen receptor modulators used as alternatives against estrogen-dependent cancers. This study aims to evaluate the antiestrogenic effects of Anthonotha macrophylla, a plant used to treat cancer in Cameroon. Methods The estrogenic/antiestrogenic activities of A. macrophylla aqueous extract were evaluated in vitro using MCF-7 cell proliferation assay. Moreover, a classical uterotrophic test was carried out to evaluate the antiestrogenic effects of A. macrophylla in rats. Changes in the uterus, vagina, and mammary glands were used as endpoints of estrogenicity. Results Anthonotha macrophylla induced antiestrogenic effects in vitro at all the tested concentrations by inhibiting estradiol-induced MCF-7 cell proliferation (p < 0.001). In vivo, a coadministration of estradiol with A. macrophylla extract led to the decrease of uterine [150 (p < 0.05) and 300 (p < 0.01) mg/kg body weight (BW)] and vaginal [75 (p < 0.01) and 300 (p < 0.05) mg/kg BW] epithelial thickness. In addition, a reduction in the mammary gland acini lumen's diameter was also observed at 75 and 150 mg/kg. Gas chromatography-time-of-flight-mass spectrometry analysis showed that phenolic acid derivatives are present in A. macrophylla extract, which are well known to be endowed with estrogenic/antiestrogenic properties. The LD50 of A. macrophylla was estimated to be less than 2000 mg/kg. Conclusions Anthonotha macrophylla aqueous extract has antiestrogenic properties. This could promote more studies to explore its ability to prevent estrogen-dependent cancers.