eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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SCImago Journal & Country Rank
3/2023
vol. 27
 
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abstract:
Original paper

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

Mariam Hamad
1
,
Radwa Ali Mehana
2
,
Mohammad M. Abd-Al haseeb
3
,
Maha Houssen
1

  1. Biochemistry Department Faculty, Pharmacy Damanhour University, Egypt
  2. Medical Physiology Department, Faculty of Medicine, Alexandria University, Egypt
  3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Damanhour University, Egypt
Contemp Oncol (Pozn) 2023; 27 (2): 198–210
Online publish date: 2023/12/21
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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.

keywords:

colon cancer, regorafenib, all-trans retinoic acid, angiogenesis, VEGF, Ki-67

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