Abstract
Purpose: To investigate the potential chemo-sensitizing effect of aged garlic extract (AGE) on doxorubicin (DOX) in breast cancer cells (MCF-7), and the possible underlying mechanisms.Methods: Human breast cancer cell line (MCF-7) was treated with AGE and DOX. The cytotoxic effects of AGE and DOX were investigated via cell cycle analysis and apoptosis induction, using flow cytometry. Mechanistic studies involved the determination of cellular uptake of DOX and p-glycoprotein (P-gp) activity.Results: Combined treatment of MCF7 cells with AGE and DOX produced no significant effect at AGE dose of 10 mg/mL. However, co-treatment with AGE at doses of 50 and 93 mg/mL enhanced the cytotoxicity of DOX on MCF-7 cells, with IC50 values of 0.962 and 0.999 μM, respectively, whencompared with 1.85 μM DOX alone. Moreover, Annexin V-FITC and PI techniques showed that AGE significantly increased percentage of cells in late apoptosis. Besides, AGE-DOX treatment significantly increased cellular uptake of DOX and inhibited P-gp activity, when compared with DOX alone (p < 0.05).Conclusion: AGE enhances the cytotoxic effect of DOX on MCF-7 cells, most likely due to cell cycle distribution, stimulation of apoptosis, increased uptake of DOX by MCF7, and inhibition of P-gp activity.
 Keywords: Aged garlic extract, Doxorubicin, Breast cancer, MCF-7 cell line, P-glycoprotein, Apoptosis, Cell cycle
Highlights
Breast cancer (BC) is the most prevalent malignancy in women worldwide
The first line chemotherapeutic drug used for BC is doxorubicin (DOX) which is a broad spectrum anthracycline antibiotic against lymphomas, leukemia, and solid tumors [3]
Late Apop Early Apop Late Apop compared to MCF-7/DOX cells. This effect was concentration-dependent, since Aged garlic extract (AGE) at a concentration of 50 mg/mL, increased intracellular Rh123 by about 3.8 folds, while AGE at a concentration of 100 mg/mL, had a more prominent effect, being able to cause > 6-fold increase of Rh123 accumulation, when compared to the control value. These results suggest that P-gp active outward transport was inhibited by AGE
Summary
Breast cancer (BC) is the most prevalent malignancy in women worldwide. The worldwide incidence of the BC is on the rise [1]. Compared with other garlic products, AGE is the most useful garlic preparation used as an antioxidant [5] It exerts cytotoxic properties in a wide variety of tumor cells, including gastric and colon cancer cells [8]. The MCF7 cell line was isolated by Dr Soule and his colleagues in 1973 from the pleural effusion of elderly patient with metastatic breast carcinoma at the Michigan Cancer Foundation. This cell line is accepted globally as an appropriate model for use in the evaluation of the anticancer effects of drugs [9]. Values of p 0.05 were used as criteria for statistical significance of differences
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
