title: 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.
authors.affiliation: Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (Indian Council of Medical Research), Uttar Pradesh, India.
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mahata
authors.forename: Arvind
authors.initials: A
authors.lastname: Pandey
authors.forename: Shirish
authors.initials: S
authors.lastname: Shukla
authors.forename: Abhishek
authors.initials: A
authors.lastname: Tyagi
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
authors.forename: Bhudev Chandra
authors.initials: BC
authors.lastname: Das
authors.forename: Alok Chandra
authors.initials: AC
authors.lastname: Bharti
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D005638:Fruit / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D027383:Papillomaviridae / Q000187:drug effects* / Q000235:genetics; D029842:Phyllanthus emblica / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1