Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells.

Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2017 Dec 07;: Authors: Wu Q, Deng J, Fan D, Duan Z, Zhu C, Fu R, Wang S 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 apoptos...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research