Abstract
Background: Doxorubicin chemotherapy may induce the development of resistance in the cancer cells. Overexpression of P-glycoprotein (P-gp) has prominent causative role in this process. Unfortunately, many inhibitory agents do not exert satisfying clinical outcome to overcome resistance. Quercetin, a polyphenolic compound, can be developed as P-gp inhibitor due to its cytotoxic properties.Objective: To investigate the effect of quercetin and doxorubicin combination in inhibiting the development of resistance in MCF-7 cell.Methods: Doxorubicin resistant MCF-7 cell were developed from the parent MCF-7 cell by exposing to 75 nM doxorubicin for 25 days. The inhibitory effect of resistance was evaluated via exposured to 75 nM doxorubicin and 750 nM quercetin combination in the same manner with resistance induction. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) citotoxicity assay and flowcytometry assay were performed to investigate the degree of resistance and to inhibit the development of resistance.Results: The exposure of 75 nM doxorubicin in MCF-7 cells (MCF-7 cells/dox75) exhibited sensitivity significantly decrease and upregulation of P-gp expression. The combination of 750 nM quercetin and 75 nM doxorubicin (MCF-7 cells/ dox75q750) caused a significantly increase in cell sensitivity to doxorubicin (p<0,05) and a decrease in P-gp expression (p> 0,05).Conclusions: The exposure of 75 nM doxorubicin led to the development of doxorubicin-acquired resistance MCF-7 cell. The combination of quercetin and doxorubicin have potency to inhibit the development of doxorubicin-acquired resistance MCF-7 cell by increasing cell sensitivity and reducing P-gp expression level.Bangladesh Journal of Medical Science Vol.16(1) 2017 p.91-97
Highlights
Doxorubicin is an anthracycline antibiotic which is considered as an effective chemotherapeutic agent for breast cancer, its usage is restricted for its cardiotoxicity and resistance.[1]
Increased P-glycoprotein (P-gp) level contributes to the development of resistance that leads to poor therapeutic outcome.[2]
We have evaluated the effect of quercetin and doxorubicin combination in preventing the development of resistance by evaluating the sensitivity of MCF-7 cell and expression of P-gp in MCF-7 cell
Summary
Doxorubicin is an anthracycline antibiotic which is considered as an effective chemotherapeutic agent for breast cancer, its usage is restricted for its cardiotoxicity and resistance.[1]. The hopes of developing P-gp modulator that could act with high degree of selectivity and low degree of toxicity has directed many investigators’ research focus onto polyphenolic compounds. One of those potential compounds to restore chemotherapy resistance is quercetin. Objective: To investigate the effect of quercetin and doxorubicin combination in inhibiting the development of resistance in MCF-7 cell. The combination of 750 nM quercetin and 75 nM doxorubicin (MCF-7 cells/ dox75q750) caused a significantly increase in cell sensitivity to doxorubicin (p 0,05). The combination of quercetin and doxorubicin have potency to inhibit the development of doxorubicin-acquired resistance MCF-7 cell by increasing cell sensitivity and reducing P-gp expression level
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