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Targeting Heat Shock Protein 27 and Fatty Acid Oxidation Augments Cisplatin Treatment in Cisplatin-Resistant Ovarian Cancer Cell Lines.
Heiserman, James Patrick; Minhas, Zenab; Nikpayam, Elahe; Cheon, Dong-Joo.
Afiliação
  • Heiserman JP; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA.
  • Minhas Z; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA.
  • Nikpayam E; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA.
  • Cheon DJ; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA.
Int J Mol Sci ; 24(16)2023 Aug 10.
Article em En | MEDLINE | ID: mdl-37628819
ABSTRACT
Most ovarian cancer patients develop recurrent cancers which are often resistant to commonly employed chemotherapy agents, such as cisplatin. We have previously shown that the inhibition of heat shock protein 27 (HSP27) or fatty acid oxidation (FAO) sensitizes cisplatin-resistant ovarian cancer cell lines to cisplatin and dual inhibition of both HSP27 and FAO induces substantial cell death in vitro. However, it is unclear how HSP27 and FAO promote cisplatin resistance, and if dual inhibition of both HSP27 and FAO would augment cisplatin treatment in vivo. Here we showed that HSP27 knockdown in two cisplatin-resistant ovarian cancer cell lines (A2780CIS and PEO4) resulted in more ROS production upon cisplatin treatment. HSP27-knockdown cancer cells exhibited decreased levels of reduced glutathione (GSH) and glucose6phosphate dehydrogenase (G6PD), a crucial pentose phosphate pathway enzyme. ROS depletion with the compound N-acetyl cysteine (NAC) attenuated cisplatin-induced upregulation of HSP27, FAO, and markers of apoptosis and ferroptosis in cisplatin-resistant ovarian cancer cell lines. Finally, inhibition of HSP27 and FAO with ivermectin and perhexiline enhanced the cytotoxic effect of cisplatin in A2780CIS xenograft tumors in vivo. Our results suggest that two different cisplatin-resistant ovarian cancer cell lines upregulate HSP27 and FAO to deplete cisplatin-induced ROS to attenuate cisplatin's cytotoxic effect.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino Limite: Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino Limite: Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article