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Peningkatan Efek Sitotoksik Doxorubicin Oleh Naringenin pada Sel Kanker Payudara T47D Melalui Induksi Apoptosis (Increased Cytotoxic Effect of Domorubicin by Naringenein on T47D Cancer Cells through Apoptosis Induction)
Abstract: Doxorubicin is one of the standard regiment for breast cancer chemotherapy, but resistance to this agent is often occured and long period usage will induce cardiotoxicity. Therefore, combination therapy (eo-chemotherapy) is needed to improve the efficacy of doxorubicin and to reduce its systemic toxicity. Naringenin is one of the most abundant flavonoids in citrus fruits which showed cytotoxicity in various human cancer cell lines and has mechanisms through pathways except p53. This research is aimed to examine the effect of naringenin in combination with doxorubicin against T47D breast cancer cell which is resistant to doxorubicin due to ps3 mutation. The IC,o dan Cl (combination index) values were determined by the MTT assay. The apoptotic stimulation effect of narigenin and doxorubicin was performed by DNA staining using ethidum bromide-acridine orange. Naringenin and doxorubicin exhibited cytotoxic effect with lC,o of 509 J.lM and 15 nM, respectively. The Cl value in all ratios of naringenin-doxorubicin showed synergistic effect (Cl 0.20-0.89). Combination of naringenin-doxorubicin with concentration smaller than 12.5 J.lM-0.6 nM in 1:1 ratio exhibited an additive combination effect. The combined treatment increased the apoptotic effect of doxorubicin. These results show that naringenin is potential to be developed as eo-chemotherapeutic agent with doxorubicin, although the molecular mechanism is still needed to be explored.
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