(+)-Usnic Acid Inhibits Migration of c-KIT Positive Cells in Human Colorectal Cancer.

(+)-Usnic Acid Inhibits Migration of c-KIT Positive Cells in Human Colorectal Cancer. Evid Based Complement Alternat Med. 2018;2018:5149436 Authors: Wu W, Hou B, Tang C, Liu F, Yang J, Pan T, Si K, Lu D, Wang X, Wang J, Xiong X, Liu J, Xie C Abstract Inhibition of tumor cell migration is a treatment strategy for patients with colorectal cancer (CRC). SCF-dependent activation of c-KIT is responsible for migration of c-KIT positive [c-KIT(+)] cells of CRC. Drug resistance to Imatinib Mesylate (c-KIT inhibitor) has emerged. Inhibition of mTOR can induce autophagic degradation of c-KIT. (+)-usnic acid [(+)-UA], isolated from lichens, has two major functions including induction of proton shuttle and targeting inhibition of mTOR. To reduce hepatotoxicity, the treatment concentration of (+)-UA should be lower than 10 μM. HCT116 cells and LS174 cells were employed to investigate the inhibiting effect of (+)-UA (<10 μM) on SCF-mediated migration of c-KIT(+) CRC cells. HCT116 cells were employed to investigate the molecular mechanisms. The results indicated that firstly, 8 μM (+)-UA decreased ATP content via uncoupling; secondly, 8 μM (+)-UA induced mTOR inhibition, thereby mediated activation suppression of PKC-A, and induced the autophagy of the completed autophagic flux that resulted in the autophagic degradation and transcriptional inhibition of c-KIT and the increase in LDH release; ultimately, 8 μM (+)-UA inhibited SCF-mediated m...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research