alexa Investigation Of The Antitumor Activity Of Cisplatin Loaded Long-circulating And PH-sensitive Liposomes In A Breast Cancer Animal Model
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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3rd World Congress on Cancer Science & Therapy
October 21-23, 2013 DoubleTree by Hilton Hotel San Francisco Airport, CA, USA

Franco M. S, Teixeira C. S, Silveira J. N, De Barros A. L. B and Oliveira M. C
Accepted Abstracts: J Cancer Sci Ther
DOI: 10.4172/1948-5956.S1.030
Abstract
The oncogenic transcription factor Forkhead Box M1 (FOXM1), which is over expressed in a wide range of human cancers, was reported to protect cancer cells from the adverse effects of oxidative stress (via trans-activation of ROS scavengers) and DNA-damage. Oxidative stress and DNA-damaging chemotherapeutic agents are commonly used in anticancer treatments. Following oxidative stress or DNA damage FOXM1 protein levels are often elevated. In this study, we sought to investigate the potential role of FOXM1 in programmed cell death induced by DNA-damage and ROS inducers. Human cancer cells after FOXM1 suppression were subjected to doxorubicin or γ-irradiation treatment. Our findings indicate that FOXM1 downregulation by stable or transient knockdown by RNAi or by treatment with proteasome inhibitors that target FOXM1 strongly sensitized human cancer cells of different origin to DNA-damage induced apoptosis. We also show that RNAi-mediated knockdown of FOXM1 or treatment with proteasome inhibitors further elevated intracellular ROS levels and increased sensitivity of cancer cells to ROS-mediated cell. In addition, we show evidence that FOXM1/proteasome inhibitor bortezomib in combination with ROS inducer PEITC efficiently inhibited the growth of breast tumor xenografts in nude mice. We demonstrated that FOXM1 partially inhibits apoptosis by suppression of the activation of pro-apoptotic JNK and activation anti-apoptotic Bcl-2. Since FOXM1 is widely over-expressed in human cancers, our data further support the notion that FOXM1 is a valid target for combinatorial anticancer therapy.
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