Design, synthesis and X‐ray structural studies of novel [acetonitrile‐benzyl‐3‐N‐(2, 4 dihydroxyphenylmethylene) hydrazinecarbodithioato‐κ3‐N′, S, O] nickel(ll) complex that potently inhibit cell proliferation through regulation of apoptosis related genes

Abstract

Nickel is a fundamental element for healthy life for human and higher animals. For biological importance, its complexation with bioactive ligand is worth to be studied with the aim to understand its function. Using mouse peritoneal cancer model, MTT colorimetric assay and anticancer activity analysis, we examined the role of nickel(ll) complex in growth inhibition of cancer cells. A novel nickel(ll) complex was synthesized and characterized using physico‐chemical and spectroscopic techniques. The study indicated that both the ligand and complex were capable of inhibiting Ehrlich Ascites Carcinoma (EAC) cells growth by 28.21% and 44.52%, respectively, when administered 0.3 mg/kg/day body weight intraperitoneally for five consecutive days in Swiss Webstar mice. Determination the LD50 of the complex (55 mg/kg) allowed adjusting the dose as 2.75 mg/kg and upon administration, inhibition increased to 69.36%. The ligand and complex have shown an inhibitory effect in the range of 4.86%–67.3% and 6.1%‐ 89.37%, respectively, against EAC cells (concentration range of 31.25–500 μg/ml) in RPMI‐1640 medium as determined by MTT colorimetric assay. Apoptotic cell morphological alteration was determined through optical and fluorescence microscopy. Up regulation of P53, Bax, Cas‐8, Cas‐3 and Fas and down regulation of NF‐kB and Bcl‐2 gene expression were observed in the cells treated with the nickel(ll) complex for five consecutive days. In conclusion, the newly synthesized nickel(ll) complex has shown anti‐proliferative activity and can further be optimized to be used as a lead molecule for anticancer drug.

A comparative study of biological potentiality and EAC cell growth inhibition activity of Phyllanthus acidus (L.) fruit pulp and seed in Bangladesh

“…Apoptotic morphological alterations such as fragmented nuclei and nuclear condensation among the neighboring cells have been observed by fluorescence microscopy in treated groups compared to the control group ( Al-Mamun et al, 2016a ). Besides, more condensed and fragmented nuclei have been found in case of MEPA fruit pulp treated EAC cell images rather than the seed extract which may be due to the initiation of EAC cell apoptosis ( Hasan et al, 2019 , Zahan et al, 2019 ). These results indirectly indicate that lectin-like proteins present in Phyllanthus acidus fruit pulp and seed extract may be responsible for the induction of morphological alterations of EAC cells ( Islam et al, 2014 , Singh et al, 2017 ).…”

“…Ehrlich’s Ascites Carcinoma (EAC) cells are commonly used in the field of ascitic tumor research worldwide due to the fastest-growing capacity and the easiest transferrable property ( Rajkapoor et al, 2007 , Zahan et al, 2019 ). Initial inoculum of EAC cells was provided by the Indian Institute of Chemical Biology (IICB), Kolkata, India.…”

Antiproliferative Activity and Apoptotic Efficiency of Syzygium cumini Bark Methanolic Extract against EAC Cells In Vivo

“…However, the DNA extracted from control mice showed a relatively unique and distinct band. The activation of the endogenous Ca 2+/ Mg 2+ dependent endonucleases mediated the cleavage of inter-nucleosomes and generated oligonucleotide fragments, which is the most distinctive biochemical hallmark of apoptosis [25]. Thus, the appearance of fragmented bands in agarose gel implies the induction of apoptosis in EAC cells by SCBME treatment.…”

Methanolic Bark Extract of Abroma augusta (L.) Induces Apoptosis in EAC Cells through Altered Expression of Apoptosis Regulatory Genes

“…e percentage of hemolysis was calculated by dividing sample absorbance on positive control absorbance (complete hemolysis) multiplied by 100. [27]. For experiment, 200 μl of EAC cells (1 × 10 6 cells) cultured in RPMI-1640 media was taken in each well of a 96-well culture plate at different concentrations (500, 250, 125, 62.5, and 31.25 μg/ml) of extract.…”