Combination Therapy of TRAIL and Thymoquinone Induce Breast Cancer Cell Cytotoxicity-Mediated Apoptosis and Cell Cycle Arrest

Abstract

Objective: Cancer is one of the leading causes of mortality in both developed and developing nations. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is characterized by its ability to selectively trigger apoptosis in cancer cells. TRAIL-based interventions have led to the development of recombinant human (rhTRAIL) as a promising therapy for different types of human cancer. Thymoquinone (TQ) has been shown to exert anticancer effect. The aim of the current study is to investigate the anticancer effect of the combinatorial therapy of TRAIL+TQ against human breast cancer cells. Methods: To achieve this hypothesis, cytotoxicity using MTT assay, as well as apoptosis and cell cycle using flow cytometric technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results: The current study showed that TRAIL induced cell cycle arrest and apoptosis. Moreover, it inhibited proliferation of MDA-MB-231 cells more than MCF-7 cells. Adding TQ to TRAIL increased the chemo-sensitivity of MDA-MB-231, while overcame the MCF-7 resistance to TRAIL. Conclusion: In conclusion, there is a synergistic effect between TRAIL and TQ playing a therapeutic role in killing resistant breast cancer cells.

Fabrication of Poly Dopamine@poly (Lactic Acid-Co-Glycolic Acid) Nanohybrids for Cancer Therapy via a Triple Collaboration Strategy

“…Many clinical cases usually show poor outcomes and efficacy to chemotherapy due to rapidly acquired resistance and distant metastases [3][4][5]. Therefore, new therapeutic strategies, such as combination therapy, which can sensitize tumor cells to chemotherapy, hold great promise for overcoming the current challenges in breast cancer treatment [6][7][8][9].…”

Design, synthesis, in vitro anticancer, molecular docking and SAR studies of new series of pyrrolo[2,3-d]pyrimidine derivatives

“…DR4 and DR5 (TRAILs receptors) are known to persuade apoptosis in an extensive variety of cancer cells, but rarely in normal cells. Normal cells are supposed to be resistant to TRAIL because their cell surface has the aptitude to express upper levels of TRAIL decoy receptors DcR1 and/or DcR2 [ 55 , 56 ]. In addition, TRAIL death receptors are known to be transcriptionally up-regulated by p53.…”