Thiosemicarbazone Derivative Induces in vitro Apoptosis in Metastatic PC-3 Cells via Activation of Mitochondrial Pathway

Title:Thiosemicarbazone Derivative Induces in vitro Apoptosis in Metastatic PC-3 Cells via Activation of Mitochondrial Pathway

Volume: 17 Issue: 5

Author(s): Saravana Kumar Sinniah, Kong Wai Tan, Seik Weng Ng and Kae Shin Sim*

Affiliation:

• Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur,Malaysia

Keywords: Thiosemicarbazone, Schiff base, MTT, apoptosis, annexin V/PI, cell cycle, mitochondrial membrane potential.

Abstract: Background: Thiosemicarbazone (TSC) is a Schiff base that has been receiving considerable attention owing to its promising biological implication and remarkable pharmacological properties. The most promising drug candidate of this class would be Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) which has entered phase II clinical trials as a potent anti-cancer chemotherapeutic agent.

Objective: The current research aimed to synthesize several Schiff base ligands from (3-formyl-4-hydroxyphenyl) methyltriphenylphosphonium (T). Additionally, the current research aimed to study the growth inhibitory effect of triphenylphosphonium containing thiosemicarbazone derivatives on PC-3 cells by deciphering the mechanisms involved in cell death.

Method: The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR, HRESIMS and X-ray crystallography) and the results were in conformity with the structure of the targeted compounds. Growth inhibitory effect of the compounds were performed against six human cell lines.

Results: DM(tsc)T displayed most potent activity against PC-3 cells with IC50 value of 2.64 ± 0.33 μM, surpassing that of the positive control cisplatin (5.47 ± 0.06 μM). There were marked morphological changes observed in DM(tsc)T treated cells stained with acridine orange and ethidium bromide which were indicative of cell apoptosis. Treatment with DM(tsc)T showed that the cell cycle is arrested in the G0/G1 phase after 72 hours. Mitochondrial membrane potential loss was observed in cells treated with DM(tsc)T, indicating the apoptosis could be due to mitochondria mediated pathway.

Conclusion: This study indicates that DM(tsc)T would serve as a lead scaffold for rational anticancer agent development.

Cite this article as:

Sinniah Kumar Saravana, Tan Wai Kong, Ng Weng Seik and Sim Shin Kae*, Thiosemicarbazone Derivative Induces in vitro Apoptosis in Metastatic PC-3 Cells via Activation of Mitochondrial Pathway, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (5) . https://dx.doi.org/10.2174/1871520616666160926110929

DOI https://dx.doi.org/10.2174/1871520616666160926110929	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992