Cytotoxic activity of the novel heterocyclic compound G-11 is primarily mediated through intrinsic apoptotic pathway

Ayman M. Saleh, Mohammad A. Aziz, Ibrahim M. Abdou, Mutasem O. Taha, Mahmoud A. Al-Qudah, Mohammed M. Abadleh, Ahmad Aljada, Syed A. Rizvi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Natural and chemically synthesized heterocyclic compounds have been explored for their potential use as anticancer agents. We had synthesized non-natural heterocyclic analogs and evaluated their anti-tumor activity by measuring effect on cell proliferation and induction of apoptosis in different cell lines. Previously, we identified a pyrazole-containing compound (G-11) showing cytotoxic effect towards leukemia and lymphoma cell lines. In this study, we further investigated the mechanistic aspects of anticancer properties of G-11 in HL-60 cell line. We demonstrated that cytotoxic effect of G-11 is mediated by caspase-dependent apoptosis. However, the involvement of mitochondrial dysfunction induced by G-11 was independent of caspases. G-11 triggered generation of ROS, caused disruption of mitochondrial transmembrane potential, increased release of cytochrome c to the cytosol, and altered the expression of Bcl-2 and Bax proteins. These results suggest significant involvement of intrinsic apoptotic pathway. This study comprehensively details the possible mechanisms of action of a novel heterocyclic compound which could find its potential use as an anticancer agent.

Original languageEnglish
Pages (from-to)873-886
Number of pages14
Issue number7
Publication statusPublished - Jul 1 2016


  • Anti-cancer
  • Apoptosis
  • Bax
  • Bcl-2
  • Heterocyclic pyrazole N-nucleosides
  • Mitochondria dysfunction
  • ROS

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research


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