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. 2008 Mar 7;14(9):1378-82.
doi: 10.3748/wjg.14.1378.

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

Toshie Okada  1 , Tokihiko Sawada, Tatsushi Osawa, Masakazu Adachi, Keiichi Kubota
Affiliations

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

Toshie Okada et al. World J Gastroenterol. .

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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Figures

Figure 1
Figure 1
Growth inhibition of pancreatic cancer cells by MK615. MK615 significantly inhibited the growth of PANC1, PK1, and PK45H cells in a dose-dependent manner (aP < 0.05). Cells were cultured for 48 h. The assay was carried out in triplicate.
Figure 2
Figure 2
Lysis of pancreatic cells by MK615. MK615 lysed PANC1, PK1, and PK45H cells at concentrations of 150, 300, and 600 μg/mL. The percentage cytotoxicities at 150, 300, and 600 μg/mL MK615 were significantly higher than those at 0 μg/mL MK615 (aP < 0.05). Cells were cultured for 48 h. The assay was carried out in triplicate.
Figure 3
Figure 3
Dual inhibition of mRNA expression of Aurora A and Aurora B kinases by MK615. MK615 significantly inhibited the transcription of Aurora A and Aurora B mRNA. The percentage inhibition in PANC1, PK1, and PK45H cells was statistically significant (aP < 0.05). RNA was extracted from the cells cultured with MK615 at a concentration of 300 μg/mL for 48 h.
Figure 4
Figure 4
Inhibition of protein expression of Aurora A and Aurora B kinases, and NF-κB by MK615. MK615 dually inhibited the expression of Aurora A and Aurora B kinases in PANC1 and PK45H cells. However, no inhibition was evident in PK1 cells. NF-κB inhibition was more evident when anti-phosphorylated NF-κB antibody was used. Protein was extracted from the cells cultured with MK615 at a concentration of 300 μg/mL for 48 h.
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References

    1. Adachi M, Suzuki Y, Mizuta T, Osawa T, Adachi T, Osaka K, Suzuki K, Shiojima K, Arai Y, Masuda K, et al. The Japanese apricot Prunus mume Sieb. et Zucc (ume) is a rich natural source of novel anti-cancer substance. Int J Food Prop. 2007;10:375–384.
    1. Nakagawa A, Sawada T, Okada T, Ohsawa T, Adachi M, Kubota K. New antineoplastic agent, MK615, from UME (a Variety of) Japanese apricot inhibits growth of breast cancer cells in vitro. Breast J. 2007;13:44–49. - PubMed
    1. Okada T, Sawada T, Osawa T, Adachi M, Kubota K. A novel anti-cancer substance, MK615, from ume, a variety of Japanese apricot, inhibits growth of hepatocellular carcinoma cells by suppressing Aurora A kinase activity. Hepatogastroenterology. 2007;54:1770–1774. - PubMed
    1. Mori S, Sawada T, Okada T, Ohsawa T, Adachi M, Keiichi K. New anti-proliferative agent, MK615, from Japanese apricot “Prunus mume” induces striking autophagy in colon cancer cells in vitro. World J Gastroenterol. 2007;13:6512–6517. - PMC - PubMed
    1. Agnese V, Bazan V, Fiorentino FP, Fanale D, Badalamenti G, Colucci G, Adamo V, Santini D, Russo A. The role of Aurora-A inhibitors in cancer therapy. Ann Oncol. 2007;18 Suppl6:vi47–vi52. - PubMed

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