%0 Journal Article
%T Sensitization of Cervical Cancer Cells to Cisplatin by Genistein: The Role of NF B and Akt/mTOR Signaling Pathways
%A K. Sahin
%A M. Tuzcu
%A N. Basak
%A B. Caglayan
%A U. Kilic
%A F. Sahin
%A O. Kucuk
%J Journal of Oncology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/461562
%X Cervical cancer is among the top causes of death from cancer in women. Cisplatin-based chemotherapy has been shown to improve survival; however, cisplatin treatment is associated with toxicity to healthy cells. Genistein has been used as an adjunct to chemotherapy to enhance the activity of chemotherapeutic agents without causing increased toxicity. The present study was designed to investigate the effect of genistein (25£¿¦ÌM) on antitumor activity of cisplatin (250£¿nM) on HeLa cervical cancer cells. We have examined the alterations in expression of NF- B, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt protein levels in response to treatment. The combination of 25£¿¦ÌM genistein with 250£¿nM cisplatin resulted in significantly greater growth inhibition ( ). Genistein enhanced the antitumor activity of cisplatin and reduced the expression of NF- B, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt. The results in the present study suggest that genistein could enhance the activity of cisplatin via inhibition of NF-¦ÊB and Akt/mTOR pathways. Genistein is a promising nontoxic nutritional agent that may enhance treatment outcome in cervical cancer patients when given concomitantly with cisplatin. Clinical trials of genistein and cisplatin combination are warranted to test this hypothesis. 1. Introduction As of 2008, cervical cancer is the third most common cause of cancer and the fourth most frequent cause of deaths from cancer in women and more than 500,000 new cervical cancer cases and 275,000 deaths were reported worldwide [1]. Although the high incidence rate is disappointing, survival rates of these patients continue to improve with the recent developments in the treatment of this particular cancer type [1, 2]. As the number of studies investigating the application of chemotherapeutical agents as a concomitant treatment method increases, chemoradiotherapy including cisplatin is becoming the recommended method instead of radiotherapy alone [2]. Cisplatin (cis-diamminedichloroplatinum II, CDDP), is an effective agent in the treatment of cervical cancer [3]. However, its usage is limited by its toxicity and acquired chemoresistance throughout the course of treatment [4¨C6]. To this end, targeted therapies that can differentiate between tumor cells and healthy cells are being developed. A naturally occurring soybean isoflavone, genistein, could inhibit tumor growth and induce apoptosis of tumor cells without damaging the normal cells [7¨C9]. Genistein (4¡ä,5,7-trihydroxyisoflavone) has a heterocyclic diphenolic structure that is similar to estrogen, but it has a more potent
%U http://www.hindawi.com/journals/jo/2012/461562/