Int. J. Mol. Sci. 2013, 14(2), 4106-4120; doi:10.3390/ijms14024106
Article

Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines

1 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan 2 Department of Immunology, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan 3 Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan
* Author to whom correspondence should be addressed.
Received: 19 December 2012; in revised form: 15 January 2013 / Accepted: 4 February 2013 / Published: 18 February 2013
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Abstract: Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G1 phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (∆ψm) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia.
Keywords: corosolic acid; Eriobotrya japonica; leukemia cells; apoptosis; anti-proliferation; caspase

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MDPI and ACS Style

Uto, T.; Sakamoto, A.; Tung, N.H.; Fujiki, T.; Kishihara, K.; Oiso, S.; Kariyazono, H.; Morinaga, O.; Shoyama, Y. Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines. Int. J. Mol. Sci. 2013, 14, 4106-4120.

AMA Style

Uto T, Sakamoto A, Tung NH, Fujiki T, Kishihara K, Oiso S, Kariyazono H, Morinaga O, Shoyama Y. Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines. International Journal of Molecular Sciences. 2013; 14(2):4106-4120.

Chicago/Turabian Style

Uto, Takuhiro; Sakamoto, Ayana; Tung, Nguyen H.; Fujiki, Tsukasa; Kishihara, Kenji; Oiso, Shigeru; Kariyazono, Hiroko; Morinaga, Osamu; Shoyama, Yukihiro. 2013. "Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines." Int. J. Mol. Sci. 14, no. 2: 4106-4120.

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