Triterpenes From Ganoderma Lucidum Induce Autophagy in Colon Cancer Through the Inhibition of p38 Mitogen-Activated Kinase (p38 MAPK)

摘要

Medicinal mushroom Ganoderma lucidum is one of the mostnesteemed natural products that have been used in the traditionalnChinese medicine. In this article, we demonstrate that G. lucidumntriterpene extract (GLT) suppresses proliferation of human colonncancer cells HT-29 and inhibits tumor growth in a xenograftmodelnof colon cancer. These effects of GLT are associated with the cellncycle arrest at G0/G1 and the induction of the programmed cellndeath Type II–autophagy in colon cancer cells. Here, we show thatnGLT induces formation of autophagic vacuoles and upregulates ex-npression of Beclin-1 (1.3-fold increase) and LC-3 (7.3-fold increase)nproteins in colon cancer cells and in tumors in a xenograft modeln(Beclin-1, 3.9-fold increase; LC-3, 1.9-fold increase). Autophagynis mediated through the inhibition of p38 mitogen-activated pro-ntein kinase (p38 MAPK) because p38 MAPK inhibitor, SB202190,ninduces autophagy and expression of Beclin-1 (1.2-fold increase)nand LC-3 (7.4-fold increase), and GLT suppresses phosphoryla-ntion of p38 MAPK (≈60% inhibition) in colon cancer cells. Takenntogether, our data demonstrate a novel mechanism responsible fornthe inhibition of colon cancer cells by G. lucidum and suggest GLTnas natural product for the treatment of colon cancer.