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IND-2, a Quinoline Derivative, Inhibits the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress,

Swapnaa Balaji1, Rabin Neupane1, Saloni Malla1

  • 1Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.

Life (Basel, Switzerland)
|November 26, 2022
PubMed

Insights

IND-2, a novel compound, effectively inhibits prostate cancer (PC) cell growth and induces apoptosis. This research highlights IND-2 as a promising candidate for developing new PC treatments with fewer side effects.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Prostate cancer (PC) is a leading cause of cancer-related deaths in men, with current treatments facing challenges like drug resistance and adverse effects.
  • Novel therapeutic agents are urgently needed for effective PC treatment, especially for metastatic cases.
  • Condensed quinolines represent a class of natural compounds with known anticancer properties.

Purpose of the Study:

  • To evaluate the in vitro anticancer efficacy of IND-2, a novel condensed quinoline derivative, against human prostate cancer cell lines (PC-3 and DU-145).
  • To elucidate the mechanisms underlying IND-2's anti-proliferative effects, including its impact on apoptosis, mitochondrial function, and cell cycle progression.

Main Methods:

  • In vitro assays were performed on PC-3 and DU-145 prostate cancer cell lines.
  • Cell proliferation was assessed using IC50 values.
  • Apoptosis was evaluated by measuring mitochondrial membrane potential, caspase activation, Bcl-2 expression, and observing morphological changes.
  • Mitotic catastrophe, reactive oxygen species (ROS) levels, and topoisomerase IIα activity were also analyzed.

Main Results:

  • IND-2 demonstrated significant inhibition of PC-3 and DU-145 cell proliferation with IC50 values of 3 µM and 3.5 µM, respectively.
  • IND-2 induced apoptosis in PC-3 cells by decreasing mitochondrial membrane potential, increasing cleaved caspase-3, -7, and PARP, and reducing Bcl-2 expression.
  • IND-2 triggered mitotic catastrophe in PC-3 cells, elevated ROS levels in DU-145 cells, and inhibited topoisomerase IIα activity.

Conclusions:

  • IND-2 exhibits potent in vitro anticancer activity against prostate cancer cell lines through multiple mechanisms, including apoptosis induction and mitotic catastrophe.
  • The findings suggest that IND-2 has the potential to be a lead compound for developing novel and more efficacious prostate cancer therapeutics.
  • Further research into IND-2 could pave the way for new treatment strategies targeting drug-resistant and metastatic prostate cancer.
Keywords:
IND-2apoptosismitotic catastrophenatural drug discoveryoxidative stressprostate cancerquinoline derivative

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