Open AccessAged garlic extract potentiates doxorubicin cytotoxicity in human breast cancer cells
Author(s) -
Huda Mohammed Alkreathy,
Noura Farraj AlShehri,
Fatemah Omer Kamel,
Ahmed Khalaf Alghamdi,
Ahmed Esmat,
Shahid Karim
Publication year - 2020
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v19i8.15
Subject(s) - doxorubicin , apoptosis , cytotoxicity , cell cycle , mcf 7 , cytotoxic t cell , flow cytometry , annexin , pharmacology , breast cancer , chemistry , cancer cell , cancer research , cancer , chemotherapy , medicine , immunology , in vitro , biochemistry , human breast
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