alexa MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases.


Journal of Cancer Science & Therapy

Author(s): Okada T, Sawada T, Osawa T, Adachi M, Kubota K

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Abstract AIM: To investigate the anti-neoplastic effect of MK615, an anti-neoplastic compound isolated from Japanese apricot, against human pancreatic cancer cells in vitro. METHODS: Three human pancreatic cancer cell lines PANC-1, PK-1, and PK45H were cultured with MK615 at concentrations of 600, 300, 150, and 0 microg/mL. Growth inhibition was evaluated by cell proliferation assay, and killing activity was determined by lactate dehydrogenase (LDH) assay. Expression of Aurora A and B kinases was detected by real-time polymerase chain reaction (PCR) and Western blotting. Cell cycle stages were evaluated by flow cytometry. RESULTS: The growth inhibitory rates of MK615 at 150, 300, and 600 microg/mL were 2.3\%+/-0.9\%, 8.9\%+/-3.2\% and 67.1\%+/-8.1\% on PANC1 cells, 1.3\%+/-0.3\%, 8.7\%+/-4.1\% and 45.7+/-7.6\% on PK1 cells, and 1.2+/-0.8\%, 9.1\%+/-2.1\% and 52.1\%+/-5.5\% on PK45H cells, respectively (P<0.05). The percentage cytotoxicities of MK615 at 0, 150, 300, and 600 microg/mL were 19.6\%+/-1.3\%, 26.7\%+/-1.8\%, 25.5\%+/-0.9\% and 26.4\%+/-0.9\% in PANC1 cells, 19.7\%+/-1.3\%, 24.7\%+/-0.8\%, 25.9\%+/-0.9\% and 29.9\%+/-1.1\% in PK1 cells, and 28.0\%+/-0.9\%, 31.2\%+/-0.9\%, 30.4\%+/-1.1\% and 35.3+/-1.0\% in PK45H cells, respectively (P<0.05). Real-time PCR and Western blotting showed that MK615 dually inhibited the expression of Aurora A and B kinases. Cell cycle analysis revealed that MK615 increased the population of cells in G2/M phase. CONCLUSION: MK615 exerts an anti-neoplastic effect on human pancreatic cancer cells in vitro by dual inhibition of Aurora A and B kinases.
This article was published in World J Gastroenterol and referenced in Journal of Cancer Science & Therapy

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