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Molecules 2013, 18(8), 9382-9396; doi:10.3390/molecules18089382
Article

Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells

1,2,†, 3,†, 1, 1, 4, 5, 2,*  and 1,*
Received: 27 May 2013; in revised form: 26 July 2013 / Accepted: 31 July 2013 / Published: 5 August 2013
(This article belongs to the Section Metabolites)
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Abstract: Isoalantolactone, a medicinal plant-derived natural compound, is known to induce apoptosis in various cancer cell lines. However, its effect on apoptosis in prostate cancer cells has not been addressed. Thus, we examined the effects of isoalantolactone on prostate cancer cells. It was found that isoalantolactone inhibits growth of both androgen-sensitive (LNCaP) as well as androgen-independent (PC3 and DU-145) prostate cancer cells in a dose-dependent manner. Furthermore, our results indicate that isoalantolactone-induced apoptosis in prostate cancer PC3 cells is associated with the generation of ROS and dissipation of mitochondrial membrane potential (Δψm). In addition, isoalantolactone triggers apoptosis in prostate cancer cells via up-regulation of Bax, down-regulation of Bcl-2, survivin, and significant activation of caspase-3. Isoalantolactone-induced apoptosis is markedly abrogated when the cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, suggesting that the apoptosis-inducing effect of isoalantolactone in prostate cancer cells is mediated by reactive oxygen species. These findings indicate that isoalantolactone induces reactive oxygen species-dependent apoptosis in prostate cancer cells via a novel mechanism involving inhibition of survivin and provide the rationale for further in vivo and preclinical investigation of isoalantolactone against human prostate cancer.
Keywords: prostate cancer; isoalantolactone; apoptosis; reactive oxygen species prostate cancer; isoalantolactone; apoptosis; reactive oxygen species
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Rasul, A.; Di, J.; Millimouno, F.M.; Malhi, M.; Tsuji, I.; Ali, M.; Li, J.; Li, X. Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells. Molecules 2013, 18, 9382-9396.

AMA Style

Rasul A, Di J, Millimouno FM, Malhi M, Tsuji I, Ali M, Li J, Li X. Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells. Molecules. 2013; 18(8):9382-9396.

Chicago/Turabian Style

Rasul, Azhar; Di, Jun; Millimouno, Faya M.; Malhi, Mahadev; Tsuji, Ichiro; Ali, Muhammad; Li, Jiang; Li, Xiaomeng. 2013. "Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells." Molecules 18, no. 8: 9382-9396.


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