Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines

Abstract

Introduction Colorectal cancer (CRC) is a significant contributor to cancer-related mortality worldwide, ranking as the second leading cause of such deaths. Central to the progression of this malignancy is angiogenesis – a complex process orchestrated by vascular endothelial growth factor (VEGF). Regorafenib, a potent multikinase inhibitor, acts as a critical antagonist of multiple kinases involved in angiogenesis, proliferation, and metastasis. Conversely, all-trans retinoic acid (ATRA) has demonstrated compelling antitumour effects across various cancer types. This study aims to comprehensively evaluate the combined antitumour potential of ATRA and regorafenib in human colon cancer cell lines while elucidating the intricate molecular mechanisms that underlie their action. Material and methods Our investigative approach involved an enzyme-linked immunosorbent assay to meticulously analyse the levels of key players in the VEGF signalling pathway, including VEGF itself, activated protein kinase (AMPK), extracellular signal-regulated protein kinase 1 (ERK1), and nuclear factor kappa B (NF-κB). Additionally, we assessed caspase-3 activity as a fundamental marker of apoptosis. Results The combined use of ATRA and regorafenib exhibited a remarkable augmentation in both AMPK and caspase-3 activities. This was accompanied by a significant reduction in VEGF, ERK1, and NF-κB levels within human colon cancer cell lines subjected to regorafenib treatment. Conclusions Our findings underscore the remarkable antiproliferative, antiangiogenic, and proapoptotic effects resulting from the combined use of ATRA and regorafenib in the context of CRC. This modulation of tumourigenic processes is predominantly mediated through the VEGF signalling axis.

Retinoic Acid Neutralizes the Effects of Herpes Simplex Virus Type 1-Infected Cell Protein 0 (ICP0) in Retinal Pigment Epithelial Cells

“…On the other hand, Wang et al observed the RA IC50 value as 140 μM in RAW264.7 cells [ 18 ]. Hamad et al determined the IC50 value as 140 μM in Caco-2 and HCT-116 cells [ 19 ]. Dastjerdi et al found the IC50 value to be 50 μM in OVCAR-3 cells [ 20 ].…”