Re: Two articles - Apabetalone for Colon Cancer?
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posted on
Jul 09, 2021 09:19AM
Yes! It does looks promising!
Here is everything I have on apabetalone for 'Colorectal Cancer':
https://www.nature.com/articles/s41416-021-01321-0
https://www.mdpi.com/1422-0067/22/7/3352/htm(HDL angle)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166002/
https://www.ncbi.nlm.nih.gov/pubmed/30098223
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12367
https://www.mdpi.com/2072-6694/11/8/1097/htm
A recent study showed that human colon adenocarcinoma (CA) cells stably transfected with ABCA1, exhibit increased proliferative, invasive and migratory behavior, which could be inhibited by simultaneous, transgenic overexpression of ApoA-I, or by exogenous treatment with human recombinant ApoA-I [157]. This inhibition was associated with downregulation of cyclooxygenase 2 (COX-2), a known promoter of colon adenocarcinoma involved in proinflammatory processes. In the same study, apabetalone, a small molecule BET-inhibitor, used in experimental therapeutics of atherosclerosis and known to induce production of ApoA-I, reduced the ABCA1-driven proliferative and invasive behavior of CA cells [157]. Another study showed that treatment of CA cells with the ApoA-I-mimetic peptide L-4F induced G0/1 cell cycle arrest, associated with decreased expression levels of cyclins D1 and A and decreased cell viability [158]. Also, it reduced the survival of CA cells stimulated by lysophosphatidic acid (LPA), a potent bioactive phospholipid, known to decrease its free concentration in the cell culture media [158].
This is a Spanish study in which the authors propose that the upregulation of ApoA-1 by apabetalone is reponsible for reduced malignancy in colorectal cancer cells.
"Based on these results, we propose here, for the first time, the potential use of apabetalone, a stimulator of APOA1 so far only considered for CVD, as a bona fide inhibitor of colorectal cancer invasiveness."
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12367