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Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF‐7 human breast cancer cell line
Author(s) -
Aborehab Nora M.,
Elnagar Mohamed R.,
Waly Nermien E.
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22638
Subject(s) - carboplatin , apoptosis , propidium iodide , paclitaxel , mcf 7 , cancer research , cell cycle , mtt assay , breast cancer , annexin , western blot , chemistry , cancer , microbiology and biotechnology , biology , medicine , programmed cell death , cisplatin , chemotherapy , biochemistry , human breast , gene
Despite advances in treatment, breast cancer remains the widest spread disease among females with a high mortality rate. We investigated the potential effects of gallic acid (GA) as supportive therapy in the management of breast cancer. Anti‐cancer activity with GA alone or in combination with paclitaxel and/or carboplatin was assessed by MTT assay and flow cytometry using annexin V/propidium iodide. The mechanism underlying the antiproliferative effects was investigated by measuring the expression of the pro‐apoptotic marker (Bax), CASP‐3, anti‐apoptotic (Bcl‐2), and, tumor suppressor (p53) by real‐time polymerase chain reaction (RT‐PCR) and western blot analysis. Cell cycle analysis was performed for the MCF‐7 breast cancer cell line. GA, paclitaxel, and carboplatin alone or in combination arrested cell cycle progression at the G2/M phase and induced Pre‐G1 apoptosis. RT‐PCR showed that the triplet combination significantly raised P53, Bax, and CASP‐3 mRNA expression (20.1 ± 1.41, 16.6 ± 0.43, and 20.04 ± 1.61, respectively) in MCF‐7 cells when compared to single or combined treatment ( p < .0001) while anti‐apoptotic Bcl‐2 mRNA levels were decreased in all treated groups compared to untreated cells. Western blot data of tested apoptotic factors were consistent with RT‐PCR results. For the first time, we show that a minimum non‐toxic concentration of GA increased the efficacy of paclitaxel‐ and carboplatin‐induced MCF‐7 apoptotic cell death.