Pt(II)-Thiocarbohydrazone Complex as Cytotoxic Agent and Apoptosis Inducer in Caov-3 and HT-29 Cells through the P53 and Caspase-8 Pathways.

Abeer Ibrahim,Tahani Al-Muhimeed,Abeer Alobaid,Taghreed Al-Noor,Ghassan Sulaiman,Mohanad Kareem,Salim Albukhaty,Majid Jabir,Zainab Taqi,Usama Sahib

doi:10.3390/ph14060509

Abstract

In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)-thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by the Pt(II)-thiocarbohydrazone complex was associated with cell cycle arrest at the G0/G1 phase. These findings suggest that the target complex inhibited the proliferation of Caov-3 and HT-29 cells, resulting in the arrest of the cell cycle and induction of apoptosis via the stimulation of the p53 and caspase-8 pathways. The present data suggests that the Pt(II)-thiocarbohydrazone complex could also be a promising chemotherapeutic agent for other types of cancer cells.

Highlights

Introduction iationsCancer is a critical disease of interest to scientists due to its long history of being among the leading causes of death [1]
The results showed the high potential of the platinum complex to cause cell with cisplatin
The results showed theout capacity ovarian adenocarcinoma and was carried after of respective the complex to of induce thecomplex apoptosisfor pathway

Summary

Introduction

Cancer is a critical disease of interest to scientists due to its long history of being among the leading causes of death [1]. There is no single disorder representing cancer; rather, it is a collection of disorders marked by the uncontrollable outgrowth of cells. Tumors are a serious risk of lethal disease with no geographic location or organ limits; they induce an annual worldwide mortality exceeding 12.7 million individuals. Mutated genes that regulate growth and are involved in DNA repair, cell division, and death typically causes tumor diseases [2]. Cancer can occur accidentally when a portion of the genetic code is miscopied, whereas. DNA damage by chemical, viral, or radiation exposure may lead to cancer induced by the environment. Previous studies on the development of anticancer strategies include various instances related to the interactions of metal ions or metal-containing compounds with

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Results

Conclusion