Zinc(ii) complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers that trigger DNA damage-mediated p53 phosphorylation in cancer cells

Abstract

In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and [Zn(bpbp)2](ClO4)2·CH3CH2OH·H2O (2) (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex 2 demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 μM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex 2 was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex 2 was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(II) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.

Synthesis of selenazolopyridine derivatives with capability to induce apoptosis in human breast carcinoma MCF-7 cells through scavenge of intracellular ROS

“…The cell cycle distribution was monitored by flow cytometric analysis, which the method was described previously [24]. Apoptotic cells with hypodiploid DNA content were measured by quantifying the sub-G1 peak in the cell cycle pattern.…”

Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): In vitro DNA/HSA binding, cleavage and cell imaging studies

“…Interaction between small molecules and DNA is of great significance in the elucidation of the mechanisms of anticancer drugs and the screening of DNA targeted drugs [11].…”

Preparation of Prunella vulgaris polysaccharide-zinc complex and its antiproliferative activity in HepG2 cells

“…It involves in building proteins, triggering enzymes, and synthesising DNA. Liu et al demonstrated that some regulatory proteins containing zinc were important for DNA synthesis, gene expression, and induction of cell apoptosis [4]. Franklin et al reported that Zn had antitumor effects on prostate cancer cells and other types of tumors [6].…”

“…Recently, many metal-based compounds, such as Pt, Ru and Au complexes, have been found to exhibit desirable anticancer activities and used in clinic worldwide for the treatment of various cancers [2,4,5]. However, the side effects, especially toxicity and drug resistance, limit the practical application of these drugs.…”

“…However, the side effects, especially toxicity and drug resistance, limit the practical application of these drugs. Moreover, these metal ions could cause deleterious effects and unavoidably toxicity in the body [4].…”