Synergistic Effects of the Combination of Active Fractions of Red Ginger Rhizome (Zingiber officinale var. rubrum) with Doxorubicin on 4T1 Cells
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Abstract
The use of chemopreventive agents in combination with chemotherapy increases the sensitivity of cancer cells, enhances the efficacy of chemotherapy, and reduces damage to healthy tissues. Red ginger rhizomes are among the natural materials that could be created as co-chemotherapy agents. The research aims to evaluate the effect of combining active fractions from red ginger rhizome with doxorubicin on the inhibition of 4T1 breast cancer cell proliferation in vitro. The extract of red ginger rhizome was obtained by maceration in 96% ethanol and fractionated using n-hexane, ethyl acetate, and a water-methanol mixture. The cytotoxicity effect was assessed using the MTT test, while proliferation inhibition and apoptosis were evaluated using the doubling time and AO/PI staining methods. The results showed that n-hexane fraction exhibited a more effective cytotoxic effect, with an IC₅₀ value of 26 µg/mL, in contrast to the ethyl acetate and water-methanol fractions, which had IC₅₀ values of 72 µg/mL and 89 µg/mL, respectively. The n-hexane fraction has a very strong synergistic effect when combined with doxorubicin, with a Combination Index (CI) value of < 0.1. Combination (n-hexane fraction 1/8 IC₅₀ with doxorubicin 1/4 IC₅₀) can extend the doubling time, and the combination (n-hexane fraction ½ IC₅₀; doxorubicin ½ IC₅₀) can induce apoptosis. The findings of this study suggest that the n-hexane fraction of red ginger rhizome has potential as a co-chemotherapy agent in combination with doxorubicin against 4T1 breast cancer cells.
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