Preprint Article Version 1 This version is not peer-reviewed

4-Acetyl-antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 Re-Expression

Version 1 : Received: 12 July 2018 / Approved: 13 July 2018 / Online: 13 July 2018 (04:24:11 CEST)

How to cite: Bamodu, O.A.; Yang, C.; Tzeng, D.T.; Kuo, K.; Huang, C.; Deng, L.; Hsiao, M.; Lee, W.; Yeh, C. 4-Acetyl-antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 Re-Expression. Preprints 2018, 2018070223 (doi: 10.20944/preprints201807.0223.v1). Bamodu, O.A.; Yang, C.; Tzeng, D.T.; Kuo, K.; Huang, C.; Deng, L.; Hsiao, M.; Lee, W.; Yeh, C. 4-Acetyl-antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 Re-Expression. Preprints 2018, 2018070223 (doi: 10.20944/preprints201807.0223.v1).

Abstract

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, western blot, RT-PCR, and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-AAQB as evidenced by inhibited cell viability and proliferation, as well as, attenuated migration, invasion and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates FOLFOX anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324 and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

Subject Areas

4-AAQB; SOD2; hsa-miR-324; colon cancer stem cells; chemoresistance; chemosensitivity

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.