Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone

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...

Full description

Bibliographic Details
Main Authors: Abd Rahman, Noor Izzah, Tham, Chau Ling, Abd Hamid, Roslida
Format: Article
Published: Elsevier Ireland Ltd 2024
Online Access:http://psasir.upm.edu.my/id/eprint/113647/
_version_ 1848866284922470400
author Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid, Roslida
author_facet Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid, Roslida
author_sort Abd Rahman, Noor Izzah
building UPM Institutional Repository
collection Online Access
description 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 IC50 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.
first_indexed 2025-11-15T14:18:10Z
format Article
id upm-113647
institution Universiti Putra Malaysia
institution_category Local University
last_indexed 2025-11-15T14:18:10Z
publishDate 2024
publisher Elsevier Ireland Ltd
recordtype eprints
repository_type Digital Repository
spelling upm-1136472024-11-25T01:20:16Z http://psasir.upm.edu.my/id/eprint/113647/ Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone Abd Rahman, Noor Izzah Tham, Chau Ling Abd Hamid, Roslida 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 IC50 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. Elsevier Ireland Ltd 2024-08 Article PeerReviewed Abd Rahman, Noor Izzah and Tham, Chau Ling and Abd Hamid, Roslida (2024) Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone. Chemico-Biological Interactions, 399. art. no. 111151. ISSN 0009-2797; eISSN: 1872-7786 https://linkinghub.elsevier.com/retrieve/pii/S0009279724002977 10.1016/j.cbi.2024.111151
spellingShingle Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid, Roslida
Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_full Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_fullStr Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_full_unstemmed Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_short Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_sort inhibition of angiogenesis and metastasis in colorectal cancer cell lines through kras-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
url http://psasir.upm.edu.my/id/eprint/113647/
http://psasir.upm.edu.my/id/eprint/113647/
http://psasir.upm.edu.my/id/eprint/113647/