Nelfinavir, an HIV protease inhibitor, induces apoptosis and cell cycle arrest in human cervical cancer cells via the ROS-dependent mitochondrial pathway.
HIV protease inhibitors (HIV-PIs) are a class of antiretroviral drugs designed to target the viral protease. Strikingly, these drugs have also been reported to possess antitumor effect. In this study, we evaluated the activity of one HIV-PI, Nelfinavir, against human cervical cancer cells. We found that Nelfinavir inhibited the growth of cervical cancer cell lines at the lowest micromolar concentrations clinically attainable. Nelfinavir promoted apoptosis and arrested the cell cycle at G1 phase. Apoptosis is attributed to the promotion of mitochondrial reactive oxygen species (ROS) production, which results in the translocation of mitochondrial apoptosis inducing factor (AIF) to the nucleus. We further showed that Nelfinavir increased mitochondrial ROS production by decreasing manganese superoxide dismutase (MnSOD) protein levels. Taken together, our results suggest that Nelfinavir can be repositioned as a cervical cancer therapeutic.
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA; Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Tong
T
Xiang
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
Lanying
L
Du
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
Petra
P
Pham
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: b.davis.zhu@gmail.com.
Bo
B
Zhu
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA; Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China. Electronic address: sjiang@nybloodcenter.org.
Shibo
S
Jiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D019888:Nelfinavir / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D017320:HIV Protease Inhibitors; D017382:Reactive Oxygen Species; D019888:Nelfinavir
Apoptosis; Cervical cancer; HIV protease inhibitor; Nelfinavir