Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment

28Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Mutations within the tumor suppressor TP53 gene are one of the most common genetic alterations present at high frequency in human tumors and have been shown to be associated with resistance to radio-chemotherapy. The lack of the wild type TP53 gene in cancer cells could be exploited for therapeutic advantage using a sequence of two antagonistic drugs. The aim of this study was to selectively kill p53 deficient cells (FaDu and H1299) by taxol and to protect p53 wild type cells (A549) by the prior administration of nutlin-3 in comparison to certain known anticancer drugs (5-fluorouracil, camptothecin, roscovitine).Methods: Cytotoxic and cytostatic properties of 5-fluorouracil, camptothecin, roscovitine and nutlin-3 administrating alone or in combination with taxol were investigated in vitro by flow cytometry.Results: It was found that nutlin-3 induced growth arrest and protected A549 cells from taxol. FaDu and H1299 cells responded to the same treatments with mitotic arrest and massive apoptosis. Other compounds (5-fluorouracil, camptothecin and roscovitine) revealed weaker selectivity and elevated toxicity in comparison to nutlin-3.Conclusions: We propose a therapeutic strategy protecting normal cells from taxol while increasing apoptosis selectively in p53-deficient cells using nutlin-3. © 2010 Tokalov and Abolmaali; licensee BioMed Central Ltd.

References Powered by Scopus

5-Fluorouracil: Mechanisms of action and clinical strategies

4240Citations
N/AReaders
Get full text

In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

4110Citations
N/AReaders
Get full text

Multi-target therapeutics: when the whole is greater than the sum of the parts

959Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Translating p53 into the clinic

318Citations
N/AReaders
Get full text

Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ros production in endothelial cells and cardiomyocytes

241Citations
N/AReaders
Get full text

The structure-based design of Mdm2/Mdmx-p53 inhibitors gets serious

146Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Tokalov, S. V., & Abolmaali, N. D. (2010). Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment. BMC Cancer, 10. https://doi.org/10.1186/1471-2407-10-57

Readers over time

‘11‘12‘13‘14‘15‘16‘17‘18‘21‘2202468

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

53%

Researcher 4

24%

Professor / Associate Prof. 3

18%

Lecturer / Post doc 1

6%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 9

45%

Biochemistry, Genetics and Molecular Bi... 5

25%

Medicine and Dentistry 4

20%

Pharmacology, Toxicology and Pharmaceut... 2

10%

Save time finding and organizing research with Mendeley

Sign up for free
0