Antiproliferative Evaluation of Novel 4-Imidazolidinone Derivatives as Anticancer Agent Which Triggers ROS-Dependent Apoptosis in Colorectal Cancer Cell.

Molecules

College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, China.

Published: December 2022

AI Article Synopsis

  • - Colorectal cancer is a major cause of cancer deaths globally, prompting the search for new treatments, particularly novel imidazolidin-4-one derivatives.
  • - One specific compound showed significant anticancer effects against CRC cell lines HCT116 and SW620 by inducing apoptosis through the mitochondrial pathway, mainly by generating reactive oxygen species (ROS).
  • - Further studies revealed that ROS production activated the c-Jun N-terminal kinase (JNK) pathway, promoting apoptosis, while the antioxidant N-acetylcysteine (NAC) inhibited these effects.

Article Abstract

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and more therapies are needed to treat CRC. To discover novel CRC chemotherapeutic molecules, we used a series of previously synthesized novel imidazolidin-4-one derivatives to study their anticancer role in several cancer cell lines. Among these compounds, compound exhibited the best anticancer activity in CRC cell lines HCT116 and SW620. We further investigated the anticancer molecular mechanism of compound . We found that compound induced mitochondrial pathway apoptosis in HCT116 and SW620 cells by inducing reactive oxygen species (ROS) production. Moreover, the elevated ROS generation activated the c-Jun N-terminal kinase (JNK) pathway, which further accelerated apoptosis. N-acetylcysteine (NAC), an antioxidant reagent, suppressed compound -induced ROS production, JNK pathway activation, and apoptosis. Collectively, this research synthesized a series of imidazolidin-4-one derivatives, evaluated their anticancer activity, and explored the molecular mechanism of compound -induced apoptosis in CRC cells. The present results suggest that compound has a potential therapeutic role in CRC. Hence, it deserves further exploration as a lead compound for CRC treatment.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783213PMC
http://dx.doi.org/10.3390/molecules27248844DOI Listing

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