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Novel indole Schiff base β-diiminato compound as an anti-cancer agent against triple-negative breast cancer: In vitro anticancer activity evaluation and in vivo acute toxicity study

  • 0Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
Bioorganic Chemistry +

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August 31, 2024

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August 31, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

A novel β-diiminato compound effectively inhibits breast cancer cell growth by inducing cell cycle arrest and apoptosis. This promising anticancer agent shows potential for triple-negative breast cancer treatment with no observed toxicity.

Area Of Science

  • Pharmacology and Medicinal Chemistry
  • Oncology and Cancer Research
  • Biochemistry and Molecular Biology

Background

  • Breast cancer, particularly triple-negative breast cancer (TNBC), presents a significant global health challenge with limited treatment options and poor survival rates.
  • Schiff base compounds are recognized for their diverse pharmacological activities, making them attractive candidates for novel anticancer drug development.

Purpose Of The Study

  • To evaluate the anticancer potential of a novel β-diiminato compound against human breast cancer cell lines.
  • To elucidate the mechanism of action underlying the compound's anti-proliferative and cytotoxic effects.

Main Methods

  • Cell viability was assessed using MTT assays in MCF-7 and MDA-MB-231 breast cancer cells.
  • Cytotoxicity was evaluated via trypan blue exclusion and lactate dehydrogenase (LDH) release assays.
  • Mechanisms of action, including cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation, were analyzed using flow cytometry and specific staining techniques.

Main Results

  • The β-diiminato compound significantly suppressed breast cancer cell viability in a dose-dependent manner (IC50 values: 2.41 ± 0.29 µM for MDA-MB-231, 3.51 ± 0.14 µM for MCF-7).
  • The compound induced G2/M phase cell cycle arrest in MDA-MB-231 cells and triggered apoptosis, evidenced by morphological changes, phosphatidylserine externalization, MMP disruption, and increased ROS levels.
  • Biochemical and histopathological analyses revealed no significant hepatotoxicity or nephrotoxicity, indicating a favorable safety profile.

Conclusions

  • The novel β-diiminato compound exhibits potent anticancer activity against breast cancer cells, primarily through ROS-mediated mitochondrial pathways leading to cell cycle arrest and apoptosis.
  • This compound demonstrates significant potential as a candidate for anticancer drug design, particularly for triple-negative breast cancer.
  • Further preclinical and clinical investigations are warranted to explore its therapeutic efficacy and safety.

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