Prodigiosin-induced cytotoxicity involves RAD51 down-regulation through the JNK and p38 MAPK pathways in human breast carcinoma cell lines

Toxicology Letters
Chien-Hsing LuChia-Che Chang

Abstract

RAD51 is essential for homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs) in mammalian cells. RAD51 is an attractive target for anticancer drugs, given high RAD51 levels are frequently observed in many human tumors and associated with increased resistance to DSBs-inducing chemotherapeutics. Prodigiosin is a bacterial tripyrrole pigment with potent anticancer activity and also provokes DSBs. We hereby aimed to elucidate the role of RAD51 in prodigiosin-induced cytotoxicity. Prodigiosin was found to down-regulate RAD51 in multiple human breast carcinoma cell lines irrespective of p53 status. Mechanistically, prodigiosin lowered RAD51 mRNA expression, whereas blockade of proteasome-mediated degradation failed to restore RAD51 levels following prodigiosin treatment. In addition, prodigiosin triggered phosphorylation of JNK and p38 MAPK, while pharmacological inhibition of JNK or p38 MAPK attenuated prodigiosin-mediated inhibition of RAD51 mRNA expression. Lastly, cells with enforced RAD51 expression showed increased resistance to prodigiosin-induced cytotoxicity as well as inhibition of colony formation. Collectively, we conclude that RAD51 down-regulation represents one of the modes of prodigiosin's c...Continue Reading

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Citations

Feb 25, 2014·Applied Microbiology and Biotechnology·Nada StankovicJasmina Nikodinovic-Runic
Sep 18, 2012·Toxicology and Applied Pharmacology·Mu-Yun PanChia-Che Chang
Mar 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mina RyuChangJu Chun
Nov 7, 2019·International Journal of Molecular Sciences·Kai ZhaoXiujun Fan
Jun 13, 2020·Frontiers in Bioengineering and Biotechnology·Ivan GuryanovRawil Fakhrullin
Apr 8, 2020·Indian Journal of Microbiology·J C L LapendaS C Nascimento
Jun 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·San-Lang WangAnh Dzung Nguyen
Nov 4, 2020·Planta medica·Diego V WilkeLeticia V Costa-Lotufo

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