AI Article Synopsis
- This study examined the effects of soy isoflavones (genistein and ME-143) and two chemotherapy drugs (5-fluorouracil and oxaliplatin) on WNT signaling in colon cancer cells.
- ME-143 was found to be a significantly more effective inhibitor of cancer cell growth compared to genistein, particularly in the DLD1 cell line, while chemotherapy drugs showed variable effects on WNT signaling depending on the cell type.
- The findings suggest that ME-143, especially when used with traditional chemotherapy, could be a promising treatment strategy for colorectal cancer by directly inhibiting the WNT/β-catenin pathway, indicating the need for further clinical research.
Article Abstract
Background: This study tested the effect of the soy isoflavones genistein and ME-143, and two chemotherapeutic agents, 5-fluorouracil (5FU) and oxaliplatin, on WNT signaling.
Materials And Methods: Colon cancer cell lines RKO (hereditary nonpolyposis colorectal cancer type) and DLD1 (most common colorectal cancer type driven by a mutation in WNT pathway) were utilized. WNT throughput was measured using a β-catenin-responsive SuperTopFlash luciferase assay. A stabilized β-catenin construct was employed to test β-catenin involvement in the mechanism of drug activity.
Results: ME-143 was a more than 10-fold potent inhibitor of DLD1 proliferation than genistein at 3.125 μM. Genistein alone did not inhibit WNT signaling in either cell line. In RKO cells, oxaliplatin and its combination with 5FU significantly inhibited WNT throughput. Neither 5FU, oxaliplatin nor their combination inhibited WNT signaling in DLD1 cells. In both the RKO and DLD1 cell lines, ME-143 significantly reduced WNT throughput by 65-75%. The introduction of stabilized β-catenin attenuated the ME-143-dependent inhibition of the WNT/β-catenin pathway.
Conclusion: ME-143 alone and in combination with 5FU and oxaliplatin effectively inhibits the WNT/β-catenin pathway in colorectal cancer cells of diverse genetic background. β-Catenin is directly involved in the mechanism of inhibition, and clinical studies are warranted.
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| http://dx.doi.org/10.21873/anticanres.11495 | DOI Listing |
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