Abstract
Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma.
Highlights
Malignant melanoma is one of the most aggressive forms of cancer, and advanced melanoma has a very poor prognosis
GPD inhibits the growth of SK-MEL-28 cells To determine whether GPD (Figure 1A) can affect melanoma cell growth, we first investigated the effects of GPD and Rb1 on SK-MEL-28 cell proliferation
BrdU assay results showed that GPD suppressed SK-MEL-28 cell growth in a dose-dependent manner, while ginsenoside Rb1 did not exert any effect at 60 mM
Summary
Malignant melanoma is one of the most aggressive forms of cancer, and advanced melanoma has a very poor prognosis. The inhibition of B-Raf is a common therapeutic strategy, acquired resistance to such inhibitors frequently occurs, which greatly reduces further options for successful treatment. To counteract this obstacle, combination therapies with B-Raf/MEK inhibitors together with compounds that can activate the AMPK pathway have been suggested. Combination therapies with B-Raf/MEK inhibitors together with compounds that can activate the AMPK pathway have been suggested This double-edged approach may be an effective weapon against melanoma, its proof-of-concept has not been extensively demonstrated [5,6]
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