[Bis(Quinoline)Palladium (II) Chloride] Demonstrates Promising Antitumour Activity alone and in Combination with 6-Shogaol

Author(s): Md Nur Alam, Jun Q Yu, Philip Beale, Nicholas Proschogo, Farjana Akter Rupon, Masum Shahriar, Fazlul Huq

Objectives: Synthesis and antitumour activity of a palladium compound, [Bis (quinoline) palladium (II) chloride] (cod-ed as NH1) alone and in combination along with its proposed mechanism of action has been described in the present study. Materials and Methods: After synthesizing the novel compound NH1 using newly established procedure in the host laboratory, in vitro anticancer activity has been performed in seven different cancer cell lines (A2780, A2780cisR, A2780ZDO473R, HT-29, CACO-2, MCF-7 and HeLa) using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Erlich Ascites Carcinoma (EAC) cells were used to evaluate in vivo anticancer activi-ty of the synthesized compound in Swiss-albino mice model. Preliminary toxicity study was also conducted in in Swiss-albino mice model at doses of 2.5 mg/kg or 5 mg/kg. Proteomic study was conducted to reveal the underlying mecha-nism of the anticancer activity of NH1. Results: The investigated palladium compound demonstrated superiority over clinical standard cisplatin against drug resistant ovarian cancer cell lines. NH1 also demonstrates 4.4 times greater activity than cisplatin against breast cancer model. Binary sequenced combination study showed that NH1 in combination with curcumin is mostly additive to an-tagonistic. However, combination of NH1 with 6-shogaol demonstrated synergism depending on dose and sequence. Proteomic study revealed that changes in expression of 14 proteins were significantly associated with anticancer mecha-nism of NH1. In vivo anticancer activity of NH1 at a dose of 0.75 mg/kg was also evidenced from EAC model. Prelimi-nary toxicity study in Swiss-albino mice proved that NH1 is comparatively less toxic at both of the administered doses, either 2.5 mg/kg or 5 mg/kg. However, cisplatin demonstrated significant toxicity at both of the administered doses. Biochemical investigations also supported that NH1 demonstrated lesser toxicity profile towards liver or kidney com-pared to clinical standard cisplatin.