Involvement of Both Extrinsic and Intrinsic Apoptotic Pathways in Tridecylpyrrolidine-Diol Derivative-Induced Apoptosis In Vitro

Abstract

Despite the decreasing trend in mortality from colorectal cancer, this disease still remains the third most common cause of death from cancer. In the present study, we investigated the antiproliferative and pro-apoptotic effects of (2S,3S,4R)-2-tridecylpyrrolidine-3,4-diol hydrochloride on colon cancer cells (Caco-2 and HCT116). The antiproliferative effect and IC50 values were determined by the MTT and BrdU assays. Flow cytometry, qRT-PCR and Western blot were used to study the cellular and molecular mechanisms involved in the induction of apoptotic pathways. Colon cancer cell migration was monitored by the scratch assay. Concentration-dependent cytotoxic and antiproliferative effects on both cell lines, with IC50 values of 3.2 ± 0.1 μmol/L (MTT) vs. 6.46 ± 2.84 μmol/L (BrdU) for HCT116 and 2.17 ± 1.5 μmol/L (MTT) vs. 1.59 ± 0.72 μmol/L (BrdU), for Caco-2 were observed. The results showed that tridecylpyrrolidine-induced apoptosis was associated with the externalization of phosphatidylserine, reduced mitochondrial membrane potential (MMP) accompanied by the activation of casp-3/7, the cleavage of PARP and casp-8, the overexpression of TNF-α and FasL and the dysregulation of Bcl-2 family proteins. Inhibition of the migration of treated cells across the wound area was detected. Taken together, our data show that the anticancer effects of tridecylpyrrolidine analogues in colon cancer cells are mediated by antiproliferative activity, the induction of both extrinsic and intrinsic apoptotic pathways and the inhibition of cell migration.

Three-Dimensional Cultivation a Valuable Tool for Modelling Canine Mammary Gland Tumour Behaviour In Vitro

“…Such new molecules are either of natural origin or synthetically created. Examples can be chalcones and pyrrolidines, which are known for inducing apoptosis in tumour cells [39,40]. Due to the disadvantages of 2D cultures, it was necessary to develop strategies to better understand the processes taking place in tumours, such as 3D cultures.…”

“…Such new molecules are either of natural origin or synthetically created. Examples can be chalcones and pyrrolidines, which are known for inducing apoptosis in tumour cells [39,40].…”