Qian Wu, Jianjun Deng, Daidi Fan
Feb 1, 2018
Citations
1
Influential Citations
111
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Quality indicators
Journal
Biochemical Pharmacology
Abstract
Graphical abstract Figure. No caption available. ABSTRACT The use of ginsenosides in cancer therapy has been intensively investigated. The ginsenoside Rh4 (Rh4), a rare saponin obtained from Panax notoginseng, dissolves in water more readily than total saponins, making this compound easier to use in anti‐cancer pharmaceutics. Here, we investigated the antiproliferative activity and mechanisms of Rh4 in colorectal cancer, both in vivo and in vitro. A colorectal cancer xenograft model showed that Rh4 significantly inhibited tumor growth with few side effects. CCK‐8 assays, flow cytometric analysis, Western blotting and immunohistochemistry revealed that Rh4 effectively suppressed colorectal cancer cell proliferation via inducing G0/G1 phase arrest, caspase‐dependent apoptosis and autophagic cell death but was not significantly cytotoxic to normal colon epithelial cells. Furthermore, apoptosis played a dominant role in Rh4‐induced cell death, as the pan‐caspase inhibitor Z‐VAD‐FMK blocked cell death to a greater extent than the autophagy inhibitor 3‐methyladenine. Moreover, Rh4 increased reactive oxygen species (ROS) accumulation and subsequently activated the JNK‐p53 pathway. An ROS scavenger and JNK and p53 inhibitors significantly attenuated Rh4‐induced apoptosis and autophagy. Thus, the present study is the first to illustrate that Rh4 triggers apoptosis and autophagy via activating the ROS/JNK/p53 pathway in colorectal cancer cells, providing basic scientific evidence that Rh4 shows great potential as an anti‐cancer agent.