Literature DB >> 18322951

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

Toshie Okada1, Tokihiko Sawada, Tatsushi Osawa, Masakazu Adachi, Keiichi Kubota.   

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.

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Year:  2008        PMID: 18322951      PMCID: PMC2693685          DOI: 10.3748/wjg.14.1378

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


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