Anticancer Activity ofPhyllanthus emblicaLinn. (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.

Emblica officinalis (Amla) with a Particular Focus on Its Antimicrobial Potentials: A Review

“…Polyphenolic compound of EO may possess anti-HSV effects via inactivating extracellular viral particles and interfering viral biosynthesis of the host cells, thus might serve as a potential therapeutic candidate against HSV 96 . Evaluation of the effectiveness of EO extract towards transcriptional activity of human papilloma virus (HPV) revealed inhibition of DNA binding of activator protein-1 (AP-1) in both HPV16-and HPV18-positive cervical cancer cell lines 100 .…”

Phytochemistry, pharmacological activities and traditional uses of Emblica officinalis: A review

“…Anti-cancer and anti-proliferative activity E. officinalis exhibits its anticancer activities through inhibition of activator protein-1 and targets transcription of viral oncogenes responsible for development of cervical Chang et al, 1995;Bhattacharya et al, 1999 cancer thus demonstrating its potential efficacy for treatment of human papillomavirus-induced cervical cancers (Mahata et al, 2013). An in vitro cytotoxicity was performed against five human cancer cell lines and the activity was done using 100µg/ml of the ethanolic whole plant extract of E. officinalis.…”

Polyphenols derived from four indigenous Indian fruits for cancer chemoprevention and chemotherapy

“…The AP-1 inhibitory activity of the fruit was found to be species-specific. Regulation of upstream signaling events through inhibition of ERK1/2 and JNK was also observed (Mahata et al, 2013). NF-Κβ inhibition is mediated primarily through chebulagic acid, ellagic acid, corilagin and gallic acid and ultimately leads to apoptosis of the cancer cells.…”

“…Other hydrolysable tannins that have been isolated include mucic acid gallate, mucic acid lactone gallate, monogalloylglucose, digalloylglucose, putranjivain A, galloyl-HHDP-glucose, elaeocarpusin. Flavonoid constituent, quercetin is also present Yang and Liu, 2014;Mahata et al, 2013). The fruit is also rich in essential trace elements, vitamin C and several amino acids (Zhu et al, 2013).…”