ABSTRACT
AIM: The aim was to examine the anti-proliferative effect of a Withania somnifera (WS) root extract in cell cultures and nude mouse xenografts of breast cancer cell line MDA-MB-231. METHODS: WS root extract was used to treat tumor cells at concentrations up to 100 µg and for nude mouse experiments, the mice received daily WS at 300 mg/kg by oral gavage for 8 weeks. RESULTS: The WS extract reduced viability of MDA-MB-231 cells by 75% and 88% after exposure of the cells to 50 and 100 µg/mL, respectively, compared to vehicle-treated controls. WS extract caused a dose-dependent increase in the percentage of cells in the sub-G1 phase compared to untreated controls by 6% and 10% after exposure to 25 and 50 µg/mL WS extract, respectively. WS extract also inhibited proliferation of xenografted MDA-MB-231 cells. The WS extract caused reductions in xenograft size by 60% compared to the untreated control after 8 weeks of treatment. Six of ten mice in the control group showed tumor metastasis to the lung, whereas there was none in the mice treated with the WS extract. At the gene level, WS caused a 75% reduction in chemokine CCL2 expression (P < 0.05) in the xenografted tumors of the treated mice. CONCLUSION: WS root extract inhibited proliferation of breast cancer cells in vitro and in vivo and significantly reduced expression of the cytokine, CCL2. These results warrant further studies to assess the underlying molecular mechanism of the anti-tumor activity of the WS extract in breast cancer.
ABSTRACT
The cancer-preventive activity of an extract of Withania somnifera (WS) roots was examined in female transgenic (MMTV/Neu) mice that received a diet containing the extract (750 mg/kg of diet) for 10 months. Mice in the treated group (n=35) had an average of 1.66 mammary carcinomas, and mice in the control group (n=33) had 2.48, showing a reduction of 33%. The average weights of the carcinomas were 2.36 g for mice in the treated group and 2.63 g for the controls, a difference of 10%. Labeling indices for Ki67 and proliferating cell nuclear antigen marker in mammary carcinomas of the treated group were 35% and 30% lower, respectively, than those of the corresponding control group. Expression of the chemokine was reduced by 50%. These results indicate that the root extract reduced the number of mammary carcinomas that developed and reduced the rate of cell division in the carcinomas.
Subject(s)
Mammary Neoplasms, Experimental/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Plant Roots/chemistry , Receptor, ErbB-2/genetics , Receptors, Estrogen/metabolism , Withania/chemistry , Animals , Biomarkers, Tumor/metabolism , Female , Immunoenzyme Techniques , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Mammary Tumor Virus, Mouse/genetics , Mice , Mice, Transgenic , Tumor Cells, CulturedABSTRACT
The chemopreventive activity of an extract of Withania somnifera (WS) roots was examined in female Sprague-Dawley rats that received the mammary carcinogen methylnitrosourea (MNU). The dose of the extract, administered by gavage, was 150 mg/kg body weight daily for 155 days, after injection of MNU. Rats in the treated group (N=15) had an average of 3.47 tumors, and rats in the control group (N=15) had 4.53, a reduction of 23%. The average weights of tumors were 4.98 g for rats in the treated group and 6.30 g for the controls, a difference of 21%. Labeling indices for Ki67 and proliferating cell nuclear antigen (PCNA) markers in cancers of the treated group were 42% and 38% lower, respectively, than those of the corresponding indices for the control group. These results indicate that the root extract significantly reduced the rate of cell division in the mammary tumors.
