Abstract

Camptothecin (CPT) reversibly binds and stabilizes cleavable complexes formed between DNA and topoisomerase I (Top1), thereby activating many downstream signaling pathways. Although several pathways induced by CPT have been elucidated, there are additional proteins that represent targets of CPT pharmacological mechanisms and remain uncharacterized. Using two-dimensional electrophoresis analysis and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-MS/MS identification, we investigated the hepatocellular carcinoma cell line SMMC-7721 for changes of protein expression following CPT treatment. Proteomic results showed that CPT treatment caused decreased expression of galectin-1 in SMMC-7721 cells. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed mRNA expression changes in galectin-1. Protein expression levels of DNA methyltransferases (DNMTs) were downregulated in response to CPT. The DNMT inhibitor 5-aza-2'-deoxycytidine (DAC) sensitized SMMC-7721 cells to the cytotoxic effect of CPT. Our results indicate that inhibition of DNMT activity by CPT may play a role in CPT-induced cell proliferation inhibition and apoptosis.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.