Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20
Iram Fatima1, Rizwan Ahmad1, Susmita Barman1
1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Background:
The repurposing of FDA-approved drugs for anti-cancer therapies is appealing due to their established safety profiles and pharmacokinetic properties and can be quickly moved into clinical trials. Cancer progression and resistance to conventional chemotherapy remain the key hurdles in improving the clinical management of colon cancer patients and associated mortality.
Methods:
High-throughput screening (HTS) was performed using an annotated library of 1,600 FDA-approved drugs to identify drugs with strong anti-CRC properties. The candidate drug exhibiting most promising inhibitory effects in in-vitro studies was tested for its efficacy using in-vivo models of CRC progression and chemoresistance and patient derived organoids (PTDOs).
Results:
Albendazole, an anti-helminth drug, demonstrated the strongest inhibitory effects on the tumorigenic potentials of CRC cells, xenograft tumor growth and organoids from mice. Also, albendazole sensitized the chemoresistant CRC cells to 5-fluorouracil (5-FU) and oxaliplatin suggesting potential to treat chemoresistant CRC. Mechanistically, Albendazole treatment modulated the expression of RNF20, to promote apoptosis in CRC cells by delaying the G2/M phase and suppressing anti-apoptotic-Bcl2 family transcription.
Conclusions:
Albendazole, an FDA approved drug, carries strong therapeutic potential to treat colon cancers which are aggressive and potentially resistant to conventional chemotherapeutic agents. Our findings also lay the groundwork for further clinical testing.
Insights
Albendazole, an FDA-approved anti-helminth drug, effectively inhibits colon cancer growth and overcomes chemoresistance. This repurposed drug shows promise for treating aggressive and resistant colon cancers, warranting further clinical investigation.
Area of Science:
- Oncology
- Drug Repurposing
- Cancer Therapeutics
Background:
- Drug repurposing offers a faster route to clinical trials for cancer therapies due to established safety and pharmacokinetics.
- Colon cancer progression and chemotherapy resistance remain significant challenges in patient management and survival.
Purpose of the Study:
- To identify FDA-approved drugs with potent anti-colon cancer properties.
- To evaluate the efficacy of promising drug candidates in preclinical models of colon cancer, including chemoresistant cases.
Main Methods:
- High-throughput screening of 1,600 FDA-approved drugs against colon cancer cells.
- In vitro and in vivo testing of candidate drugs in colon cancer models, including patient-derived organoids and chemoresistant cells.
Main Results:
- Albendazole demonstrated significant inhibition of colon cancer cell tumorigenicity, xenograft growth, and organoid development.
- Albendazole sensitized chemoresistant colon cancer cells to 5-fluorouracil and oxaliplatin.
- Mechanistically, albendazole promoted apoptosis by modulating RNF20 expression, delaying G2/M phase, and suppressing Bcl2 family transcription.
Conclusions:
- Albendazole, an FDA-approved drug, exhibits strong therapeutic potential for aggressive and chemoresistant colon cancers.
- The findings support albendazole as a viable candidate for further clinical trials in colon cancer treatment.
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