Affiliations: [a] Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [b] Department of Molecular Medicine, Tehran University of Medical Sciences, Tehran, Iran
Correspondence:
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Corresponding authors: Soudeh Ghafouri-Fard, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: [email protected]; Elahe Motevaseli, Department %****␣hab-28-hab200405_temp.tex␣Line␣25␣**** of Molecular Medicine, Tehran University of Medical Sciences, Tehran, Iran. Tel./Fax: +98 2123872572; E-mail: [email protected].
Abstract: BACKGROUND: Recent studies have highlighted the role of natural elements in reduction of cancer cell growth and apoptosis. Koenimbine, a natural product isolated from Murraya koenigii (L) Spreng is a substance with cytotoxic effects on cancer cells. AIM: The effects of koenimbine on HT-29 and SW48 colon cancer cells were evaluated by MTT and Annexin V assays. Expression levels of Wnt/β-catenin pathway genes were quantified by real time PCR. RESULTS: The IC50 values of koenimbine in HT-29 and SW48 was calculated to be 50 μg/ml based on the results of MTT assay. This value was 75 μg/ml in IEC-18 cells which were used as normal control. Annexin V assays revealed induction of cell apoptosis and necrosis in HT-29 and SW48 cells but not IEG18 cells by koenimbine. Koenimbin treatment resulted in significant down-regulation of CYCLD1 expression in SW48 cell line, but up-regulation of this gene in HT29 cell line. Expression of TBLR1, DKK1, GSK3B and β-catenin was significantly decreased after koenimbin treatment in HT-19 cell line. Moreover, expression of DKK1 and GSK3B was significantly decreased after koenimbin treatment in SW-40 cell line. TCF4 expression was not detected in any of cell lines either before or after treatment with koenimbin. CONCLUSION: The current in vitro study showed the cytotoxic effects of koenimbin on two colon cancer cell lines and the effects of this substance on expression of selected genes from Wnt-β catenin pathway. Future in vivo studies are needed before suggestion of this substance as an anti-cancer drug.
