Publications

@article{Ahmed2019-eb,

title = {Repurposing antibacterial AM404 as a potential anticancer drug 

 for targeting colorectal cancer stem-like cells},

author = {Mehreen Ahmed and Nicholas Jinks and Roya Babaei-Jadidi and Hossein Kashfi and Marcos Castellanos-Uribe and Sean T May and Abhik Mukherjee and Abdolrahman S Nateri},

year  = {2019},

date = {2019-12-01},

journal = {Cancers (Basel)},

volume = {12},

number = {1},

pages = {106},

publisher = {MDPI AG},

abstract = {Tumour-promoting inflammation is involved in colorectal cancer 

 (CRC) development and therapeutic resistance. However, the 

 antibiotics and antibacterial drugs and signalling that regulate 

 the potency of anticancer treatment upon forced differentiation 

 of cancer stem-like cell (CSC) are not fully defined yet. We 

 screened an NIH-clinical collection of the small-molecule 

 compound library of antibacterial/anti-inflammatory agents that 

 identified potential candidate drugs targeting CRC-SC for 

 differentiation. Selected compounds were validated in both in 

 vitro organoids and ex vivo colon explant models for their 

 differentiation induction, impediment on neoplastic cell growth, 

 and to elucidate the mechanism of their anticancer activity. We 

 initially focused on AM404, an anandamide uptake inhibitor. 

 AM404 is a metabolite of acetaminophen with antibacterial 

 activity, which showed high potential in preventing CRC-SC 

 features, such as stemness/de-differentiation, migration and 

 drug-resistance. Furthermore, AM404 suppressed the expression of 

 FBXL5 E3-ligase, where AM404 sensitivity was mimicked by 

 FBXL5-knockout. This study uncovers a new molecular mechanism 

 for AM404-altering FBXL5 oncogene which mediates 

 chemo-resistance and CRC invasion, thereby proposes to repurpose 

 antibacterial AM404 as an anticancer agent.},

keywords = {AM404, cancer stem cells, colonosphere, CRC, Differentiation, drug screening, FBXL5 E3-ligase, patient derived organoids, resistance and metastasis, tissue explants},

pubstate = {published},

tppubtype = {article}

}