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Targeted Therapies and Clinical Translational Research: Combination Therapies

Inhibition of paclitaxel-resistant MCF-7 RAg cell growth by Vernonia amygdalina extract

Jackson State University, Jackson, MS

Abstract

B49

The aqueous extract of Vernonia amygdalina (V.A.), a plant native to Nigeria, has been shown to inhibit growth of various cancer cell types without harmful side effects. Since drug resistance is a major obstacle for successful anticancer therapy, combined treatment regimens which 1) render the desired anti-cancerous effects, obtain synergistic effects, and 3) allow significant dose reductions of both drugs are desirable. The objectives of this study were to determine the effects of exposure to V.A., ethanol, or a combination of V.A. and ethanol, on doxorubicin or paclitaxel-resistant MCF-7 (MCF-7 RAg) breast cancer cell growth. MCF-7 RAg cells were cultured and exposed to 100ug/ml or 300ug/ml of V.A., with either 0.3% or 3% ethanol, or a combination and cell number was determined after exposure for at the 24hr, 48hr, 72hr or 7d time points. Results indicate that treatment with V.A. extract alone led to a 30 fold decrease in cell count at each of the timepoints, and 0.3% ethanol exposure alone was stimulatory at the 7d timepoint by 50 fold. Interestingly, the most noticeable effects were observed following combined exposure at the 72 hr and 7d timepoints. Following 72 hr exposure, combined treatment led to a 30 fold decrease in the cell count compared to the effects observed following either V.A. only treatment or 0.3% ethanol only treatment. Additionally, following 7d exposure, combined led to a 50 fold decrease in cell count compared to the effect observed following V.A. only treatment, and a 70 fold decrease in cell count compared to the stimulatory effect observed following 0.3% ethanol only treatment. In that combined exposure led to enhanced inhibition, these findings indicate that V.A. treatment reverses the ethanol-induced stimulatory response in paclitaxel-sensitive human cancer cell growth, and shows that V.A. inhibits the growth of MCF-7 RAg cells in culture. Perhaps V.A. may be a useful agent against breast tumor cells which survive chemotherapy with taxol.Key Words: Vernonia amygdalina extract, anti-carcinogens, ethanol, drug resistance, and paclitaxel.Acknowledgments: This research was financially supported in part through the NIH-Project EXPORT Grant No. 5P20MD000534-02, the NIH-EARDA grant, Grant No. 1G11HDO46519-01, and through the NIH/RCMI-CEH at JSU, Grant No. 1G12RR13459. Special thanks to Dr. Ernest Izevbigie for the V. A. extract, and Dr. Mandip Sachdeva, Florida A & M University, for the MCF-7 RAg cells, both of which were provided as generous gifts.