PMID: 18196976Jan 17, 2008Paper

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and modulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

Cell Cycle
Karuppaiyah SelvendiranPeriannan Kuppusamy

Abstract

We have previously reported the inhibitory effect of NCX-4016, a nitro derivative of aspirin, on the proliferation of cisplatin-resistant human ovarian cancer cells, in vitro (Bratasz et al., Proc Natl Acad Sci USA 2006; 103:3914-9). In this report we present the results of our study on the mechanistic aspects of drug action including the molecular and signaling pathways involved in an in vitro cell line, as well as in a murine tumor xenograft. We report, for the first time, that NCX-4016 significantly inhibited the growth of cisplatin-resistant human ovarian cancer xenografts in mice. We observed that the inhibitory effect of NCX-4016 on cell proliferation was associated with G(1) phase cell cycle arrest with increased activity of p53, p21 and p27 proteins. NCX-4016 modulated the Bcl-2 family of proteins, and induced apoptosis by activating Bax and cytochrome c release in a time-dependent manner. In addition, NCX-4016 selectively down-regulated the phosphorylated forms of EGFR (Tyr845, Tyr992), pAkt (Ser473, Thr305), and STAT3 (Tyr705, Ser727), in vitro and in vivo. Taken together, the results clearly suggested that NCX-4016 causes significant induction of cell cycle arrest and apoptosis in cisplatin-resistant human ovarian ca...Continue Reading

Citations

Jun 2, 2012·Journal of Medicinal Chemistry·Bikash DebnathNouri Neamati
Mar 9, 2010·Molecular Pharmaceutics·Ellen V StevensMark H Schoenfisch
May 6, 2010·Molecular Cancer Therapeutics·Karuppaiyah SelvendiranPeriannan Kuppusamy
Apr 30, 2011·Future Medicinal Chemistry·Daniela MasciocchiDaniela Barlocco
Mar 25, 2014·BMC Systems Biology·Benjamin GarciaMichael Strong
Jul 23, 2009·International Journal of Cancer. Journal International Du Cancer·Karuppaiyah SelvendiranPeriannan Kuppusamy
Sep 3, 2009·Annals of the New York Academy of Sciences·Bharat B AggarwalBokyung Sung
Jul 14, 2016·Médecine sciences : M/S·Stéphanie PlenchetteAli Bettaieb
Oct 30, 2016·European Journal of Pharmacology·Ming ZongSen Li
May 25, 2013·International Journal of Molecular Sciences·Ken-Ichi Sato
Mar 12, 2009·The Journal of Pharmacology and Experimental Therapeutics·Karuppaiyah SelvendiranPeriannan Kuppusamy
May 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Antonia Martin-MartinRodrigo López-Muñoz
Nov 5, 2020·International Journal of Molecular Sciences·Demetra H HufnagelAlicia Beeghly-Fadiel

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