The combination of 5-fluorouracil plus p53 pathway restoration is associated with depletion of p53-deficient or mutant p53-expressing putative colon cancer stem cells.

Cancer Biology & Therapy
Catherine HuangWafik S El-Deiry

Abstract

The cancer stem cell hypothesis suggests that rare populations of tumor-initiating cells may be resistant to therapy, lead to tumor relapse and contribute to poor prognosis for cancer patients. We previously demonstrated the feasibility of p53 pathway restoration in p53-deficient tumor cell populations using small molecules including ellipticine or its derivatives. We now establish a single cell p53-regulated green fluorescent protein (EGFP)-reporter system in human DLD1 colon tumor cells expressing mutant p53 protein. We use these p53-EGFP reporter DLD1 cells to investigate the status of p53 transcriptional activity in putative colon cancer stem cell populations following exposure to p53 pathway-restoring drugs and/or classical chemotherapy. We demonstrate induction of p53-specific EGFP reporter fluorescence following overexpression of p53 family member p73 by an Adenovirus vector. We further show that p53-reporter activity is induced in DLD1 putative cancer stem cell side-populations analyzed by their Hoechst dye efflux properties following treatment with the p53 pathway restoring drug ellipticine. Combination of ellipticine with the cytotoxic agent 5-fluorouracil resulted in increased cytotoxicity as compared to either agent...Continue Reading

Citations

Jan 7, 2011·Journal of Oncology·Sanna-Maria HedeMikael S Lindström
Aug 29, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Santhi Latha PandrangiSunita Saxena
Sep 25, 2012·Expert Opinion on Therapeutic Targets·Varun V PrabhuWafik S El-Deiry
Feb 25, 2014·FEBS Letters·Ronit Aloni-GrinsteinVarda Rotter
Sep 21, 2011·Molecular and Cellular Endocrinology·Jonathan D WassermanDavid Malkin
Mar 18, 2015·Cancer Biology & Therapy·Varun V Prabhu, Wafik S El-Deiry
Aug 9, 2015·EMBO Reports·Ying-Hua Wang, David T Scadden
Jul 26, 2017·Apoptosis : an International Journal on Programmed Cell Death·Yu-Ling NiKang Fang

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