Anticancer Activity of Phyllanthus emblica Linn. (Indian Gooseberry): Inhibition of Transcription Factor AP-1 and HPV Gene Expression in Cervical Cancer Cells

Abstract

Plant products of Phyllanthus emblica Linn. are traditionally consumed for its immense nutritive and medicinal values. However, the molecular mechanism(s) by which it exerts it effects is less understood. In this study, we investigated mechanism of action of P. emblica fruit extract (PE) by studying its effect on activator protein-1 (AP-1) activity and human papillomavirus (HPV) transcription that are essential for tumorigenicity of cervical cancer cells. PE resulted in a dose-and time-dependent inhibition of DNA binding activity of constitutively active AP-1 in both HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cells. PE-induced AP-1 inhibition was found mediated through downregulation of constituent AP-1 proteins, c-Jun, JunB, JunD, and c-Fos; however, the kinetics of their inhibition varied in both the cell types. Inhibition of AP-1 by PE was accompanied by suppression of viral transcription that resulted in growth inhibition of cervical cancer cells. Growth inhibitory activity of PE was primarily manifested through induction of apoptotic cell death. These results suggest that P. emblica exhibits its anticancer activities through inhibition of AP-1 and targets transcription of viral oncogenes responsible for development and progression of cervical cancer thus indicating its possible utility for treatment of HPV-induced cervical cancers.

ACKNOWLEDGMENTS

This work was supported by the Extramural & Intramural Grant from Indian Council of Medical Research and extramural grant from Department of Biotechnology, Government of India to Alok Chandra Bharti and Bhudev Chandra Das.

Shirish Shukla is now with the Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan, USA.