The role of efflux transporters in cytotoxicity and intracellular concentration of chlorpyrifos and chlorpyrifos oxon in human cell lines.

In this study, we investigated the role of two efflux transporters, p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), in the cytotoxicity and intracellular accumulation of the organophosphate pesticide chlorpyrifos (CPF) and its active metabolite, CPF-oxon (CPFO), in a human-derived liver cell line (HepG2) and kidney epithelial cell line (HK-2). The cytotoxicity to CPF and CPFO differed between cell lines where HK-2 had lower IC50 values which could be attributed to lower basal expression and inducibility of metabolizing enzymes, transporters, and nuclear receptors in HK-2 cells. In HepG2 cells, co-exposure of CPF with a specific inhibitor of either P-gp or BCRP enhanced the cytotoxicity of CPF while co-exposure of CPFO with VRP enhanced the cytotoxicity of CPFO, suggesting the role of these transporters in the elimination CPF and CPFO.

Silencing of High Mobility Group Isoform I-C (HMGI-C) Enhances Paclitaxel Chemosensitivity in Breast Adenocarcinoma Cells (MDA-MB-468).

Purpose: HMGI-C (High Mobility Group protein Isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal protein that can modulate transcription of an ample number of genes. Genome-wide studies revealed up regulation of the HMGI-C gene in many human cancers. We suggested that HMGI-C might play a critical role in the progression and migration of various tumors.

Molecular mechanisms of apoptosis and roles in cancer development and treatment.

Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold.