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20S-Ginsenoside Rg3 sensitizes Doxorubicin-induced Cell Death via Modulation of Autophagy in HCC

Authors
Kim, Dong-Gun; Lee, Ju-Yeon; Koo, Gi-Bang; Kwon, Sung Won; Hong, Soon Sun; Kim, You-Sun
Department
Institute for Medical Sciences
Abstract
In this study, we investigated the effect of Rg3 on autophagy, and to evaluate whether such effect is relevant to the sensitization

effect of Rg3 to apoptosis induced by DNA damage agents in hepatocellular carcinoma cells. We found that that Rg3 is able to markedly increase autophagy markers in cancer cells, including GFP-LC3 punctuation and LC3 II conversion. However, Rg3

treatment led to accumulation of p62 level and addition of chloroquine failed to further enhance autophagy markers, indicating that Rg3 is likely to suppressed autophagic flux at late maturation and degradation stage. Moreover, it was also found that Rg3 exerts synergistic effect on cell death induced by a DNA-damage agent, doxorubicin in different hepatocellular carcinoma cell lines, suggesting that Rg3 sensitizes doxorubicin-induced cell death via suppression of autophagy. Using the mouse xenograft model, we confirmed that the synergistic effect of Rg3 with doxorubicin in inhibiting tumor growth. Taken together, our data suggest that the Suppression effect of Rg3 on autophagy is functionally related to its sensitization effect on doxorubicin-

induced cell death which is caspase-independent and such a combination could serve as a novel strategy for chemotherapy for HCC.
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