Lupeol induces S-phase arrest and mitochondria-mediated apoptosis in cervical cancer cells

  • Nupoor Prasad
  • Akash Sabarwal
  • Umesh C S Yadav
  • Rana P Singh
Article
  • 35 Downloads

Abstract

Cervical cancer is fourth most common fatal cancer in women worldwide. Lupeol is a dietary triterpenoid and has shown its anticancer efficacy against various cancer types with selectivity in targeting cancer cells. In the present study, anticancer efficacy and mechanism of action of a phytochemical, lupeol, in human cervical carcinoma (HeLa) cells has been examined. The anticancer efficacy of lupeol was assessed by trypan blue cell counting, annexin V assay, cell cycle analysis, expression of apoptotic proteins by RT-PCR and Western blotting and assessment of mitochondrial ROS generation by mitosox and mitotracker assays. Our results demonstrated that lupeol decreased cell proliferation and viability of HeLa cells significantly (p<0.001). Lupeol induced S-phase cell cycle arrest and also decreased the expression of S-phase Cyclins and CDKs and increased the expression of cyclin-dependent kinase inhibitors, p21 at transcriptional and translational level. Further, lupeol induced apoptosis and increased the expression of apoptosis markers such as cleaved PARP and Bax:Bcl-2 ratio. Furthermore, mitosox and mitotracker dye incubation followed by FACS analysis showed an increase in mitochondrial superoxide generation and reduction in healthy mitochondrial mass. These results suggest that lupeol could be an effective chemotherapeutic agent against cervical carcinoma due to its growth inhibitory activity through induction of S-phase cell cycle arrest and apoptosis.

Keywords

Apoptosis cell cycle cervical cancer lupeol mitochondria ROS 

Abbreviations

CDKI

cyclin-dependent kinase inhibitor

NAC

N-acetyl cysteine

PARP

poly(ADP-ribose) polymerase

ROS

reactive oxygen species

Notes

Acknowledgements

NP is recipient of UGC Non-NET Fellowship from Central University of Gujarat, Gandhinagar, UCSY is recipient of Ramanujan Fellowship from Department of Science and Technology (DST)/Science Engineering and Research Board (SERB), India.

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Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Nupoor Prasad
    • 1
  • Akash Sabarwal
    • 2
  • Umesh C S Yadav
    • 1
  • Rana P Singh
    • 2
  1. 1.School of Life SciencesCentral University of GujaratGandhinagarIndia
  2. 2.Cancer Biology Laboratory, School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia

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