Entity

Time filter

Source Type


Mahata S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Bharti A.C.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Shukla S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Tyagi A.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | And 3 more authors.
Molecular Cancer | Year: 2011

Background-: Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1) plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated.Results-: We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3.Conclusion-: These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer through inhibition of AP-1 and blocking viral oncoproteins E6 and E7 expression. Inhibition of AP-1 activity by berberine may be one of the mechanisms responsible for the anti-HPV effect of berberine. We propose that berberine is a potentially promising compound for the treatment of cervical cancer infected with HPV. © 2011 Mahata et al; licensee BioMed Central Ltd. Source


Mahata S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Pandey A.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Shukla S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Shukla S.,University of Michigan | And 5 more authors.
Nutrition and Cancer | Year: 2013

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. © 2013 Copyright Taylor and Francis Group, LLC. Source


Narain R.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Sardana S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Gupta S.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research | Sehgal A.,Institute of Cytology and Preventive Oncology Indian Council of Medical Research
National Medical Journal of India | Year: 2013

Background. The increase in tobacco use among adolescents in India is fraught with serious public health implications. The knowledge of factors which influence this habit could assist in tackling this problem. Hence, we aimed to determine factors associated with tobacco use among school students. Methods. Data on determinants of tobacco use were collected from 4786 students of classes VII to XII (age 11- 19 years) studying in the schools of Noida city, using a selfadministered questionnaire. A cluster sample design was used to produce a representative sample of schools. The classes were randomly selected and from each selected class, all students of every alternate section were included. Differences in proportions between the various groups were tested using Pearson chi-square test or Fisher exact test. Results. Of the 4786 students, 'current tobacco use' was reported by 197 (4.1%) students; 107 (2.2%) were exclusive smokers, 49 (1%) were exclusive tobacco chewers and 41 (0.9%) used both forms of tobacco. Tobacco use was less frequent among children of white collar than blue collar fathers (p<0.05) and also among children of more educated than less educated mothers (p<0.05). Tobacco use of father, mother, siblings and friends had a significant association with the student's tobacco use. The habits were 10.6-, 6.4-, 3.1- fold higher among students if they bought tobacco for teachers, brothers, father/relatives, respectively. Among tobacco users, 31.5% adopted these habits to refresh themselves, 45.9% preferred smoking outside home and 61% were influenced by actors smoking in films. Conclusions. Socioeconomic status, family and peer influence play an important role in students using tobacco. © The National Medical Journal of India 2013. Source

Discover hidden collaborations