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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00352

Dietary polyphenols, resveratrol and pterostilbene exhibit antitumor activity on an HPV E6-positive cervical cancer model An in vitro and in vivo analysis

 Kaushiki Chatterjee1, 2*,  Sumit Mukherjee1, 2, Jonathan Vanmanen2, Probal Banerjee1, 2 and  Jimmie E. Fata1, 2*
  • 1The Graduate Center, City University of New York, United States
  • 2College of Staten Island, United States

Human papilloma virus (HPV)-induced cervical cancer is one of the most frequent cancers in women residing in underdeveloped countries. Natural compounds like polyphenols continue to be of scientific interest as non-toxic effective alternative treatments. Our previous work showed the efficacy of two polyphenols, resveratrol and pterostilbene on human HeLa cells. Here we explored the in vitro anti-cancer activity and in vivo anti-tumor potential of these two structurally similar compounds on HPV oncogene E6 and E7 positive murine TC1 cells. In vitro analysis confirmed the cytotoxic potential of both resveratrol and pterostilbene compounds with each having a low IC50 value and each showing the ability to downregulate viral oncogene E6. Further in vivo studies on TC1 tumors developing in mice indicated that treatment with either resveratrol or pterostilbene can significantly inhibit tumor development, with both compounds capable of downregulating E6 and VEGF tumor protein levels. Interestingly, the decrease in tumor size in pterostilbene was associated with tumor cell apoptosis, as indicated by an upregulation of activated caspase-3 whereas in resveratrol-treated mice it was accompanied by arrest of cell cycle, as indicated by a downregulation of PCNA. Thus, resveratrol and pterostilbene can serve as potential antineoplastic agents against HPV E6+ tumors and may suppress tumor growth via two different mechanisms.

Keywords: HPV E6 positive cervical cancer, natural product, resveratrol, pterostilbene, PCNA – Proliferating Cell Nuclear Antigen, caspase-3, VEGF - vascular endothelial growth factor, in vivo

Received: 22 Jan 2019; Accepted: 17 Apr 2019.

Edited by:

David A. Gewirtz, Virginia Commonwealth University, United States

Reviewed by:

Ekaterina Dadachova, University of Saskatchewan, Canada
Amarjit Luniwal, North American Science Associates Inc., United States  

Copyright: © 2019 Chatterjee, Mukherjee, Vanmanen, Banerjee and Fata. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Kaushiki Chatterjee, The Graduate Center, City University of New York, New York City, 10016, New York, United States,
Dr. Jimmie E. Fata, College of Staten Island, Staten Island, 10314, New York, United States,