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

Abstract EN

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 migration of CRC c-KIT(+) cells.

Taken together, 8 μM could be determined as the effective concentration for (+)-UA to inhibit SCF-mediated migration of CRC c-KIT(+) cells.