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Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2024 Aug 25; Vol. 399, pp. 111151. Date of Electronic Publication: 2024 Jul 16. - Publication Year :
- 2024
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Abstract
- Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged as a potent anti-inflammatory and anti-angiogenic compound with substantial potential, as evidenced by previous studies. This study aimed to explore the potential of BQ in suppressing angiogenesis and metastasis in the human CRC cell lines LoVo and HCT116. Various in vitro and in silico studies have been conducted to elucidate the potential pathway(s) of BQ. BQ was highly cytotoxic, with an IC <subscript>50</subscript> of 7.01 ± 0.6 μM in HCT116 and 9.58 ± 0.8 μM in LoVo cells. Moreover, BQ induced notable apoptotic activity and suppressed migration, invasion, and adhesion in both cell lines. The inhibition of MMP-2 suggests the potential of BQ to impede extracellular matrix degradation and CRC cell metastasis. BQ inhibits the expression of key proteins involved in angiogenesis and metastasis, including VEGF-A, VEGF-C, BRAF, ERK, KRAS, PI3K, and AKT. Molecular docking simulations illustrated the robust binding of BQ to CRC protein receptors. BQ holds promise in impeding CRC progression by targeting angiogenesis and metastasis, particularly through inhibition of the KRAS/BRAF/ERK and KRAS/PI3K/AKT signaling pathways.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roslida Abd Hamid reports financial support and equipment, drugs, or supplies were provided by Malaysia Ministry of Higher Education. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Cell Line, Tumor
Apoptosis drug effects
Proto-Oncogene Proteins c-akt metabolism
Neoplasm Metastasis
Matrix Metalloproteinase 2 metabolism
Cell Adhesion drug effects
Angiogenesis
Colorectal Neoplasms pathology
Colorectal Neoplasms drug therapy
Colorectal Neoplasms metabolism
Benzoquinones pharmacology
Benzoquinones chemistry
Signal Transduction drug effects
Proto-Oncogene Proteins p21(ras) metabolism
Proto-Oncogene Proteins p21(ras) genetics
Cell Movement drug effects
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic pathology
Neovascularization, Pathologic metabolism
Molecular Docking Simulation
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 399
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 39025287
- Full Text :
- https://doi.org/10.1016/j.cbi.2024.111151