MK615 Suppresses Hypoxia Tolerance by Up-regulation of E-cadherin in Colorectal Cancer Cells With Mutant KRAS

• Published in: Anticancer research Vol. 40; no. 8; pp. 4687 - 4694
• Main Authors: Nishi, Kensuke, Tsunoda, Toshiyuki, Uchida, Yoshinori, Sueta, Takayuki, Sawatsubashi, Motohiro, Yamano, Takafumi, Hashiguchi, Yasuko, Swain, Anthony, Shirasawa, Senji, Sakata, Toshifumi
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01.08.2020
• Subjects: Anticancer properties; Cell culture; Colorectal cancer; Colorectal carcinoma; E-cadherin; Hypoxia; Hypoxia-inducible factor 1; K-Ras protein; Mutants; Proteins; Prunus mume; Spheroids; Up-regulation; Western blotting
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14468

Background/Aim: The Japanese apricot "Prunus mume" is a traditional Japanese medicine. MK615, a compound extract from Prunus mume has been reported to have anti-tumor effects. Herein, we used 3D floating (3DF) culture to evaluate the anticancer effects of MK615 against human colorectal cancer (CRC) cells that contain mutant (mt) KRAS. Materials and Methods: HKe3 cells exogenously expressing mtKRAS (HKe3-mtKRAS) were treated with MK615 in 3DF cultures. The protein levels of hypoxia-inducible factor 1 (HIF-1) and E-cadherin were quantified by western blotting. Results: MtKRAS enhanced hypoxia tolerance via up-regulation of HIF-1. The expression of HIF-1 protein was suppressed by constitutive overexpression of E-cadherin in CRC HCT116 spheroids. MK615 increased the expression of E-cadherin and decreased the expression of HIF-1 in HKe3-mtKRAS. These results suggest that MK615 suppresses hypoxia tolerance by up-regulation of E-cadherin in CRC cells with mtKRAS. Conclusion: MK615 exhibits properties useful for the potential treatment of CRC patients with mtKRAS.