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Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China
Dental Hospital, Jilin University, Changchun 130041, China
Jilin Province People's Hospital, Changchun 130021, China
Department of Public Health, Tohoku University, Sendai 980-8576, Japan
Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan 60800, Pakistan
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 27 May 2013; in revised form: 26 July 2013 / Accepted: 31 July 2013 / Published: 5 August 2013
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
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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.
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.
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.