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Title Induction of AHR Gene Expression in Colorectal Cancer Cell Lines by Cucurbitacin D, E, and I
Type JournalPaper
Keywords Aryl hydrocarbon receptor, Colon cancer, Cucurbitacin, HT-29, SW-480
Abstract Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and its induction may result in suppressing of cell proliferation in colorectal cancer (CRC). Cucurbitacin D (CucD), E (CucE) and I (CucI) are plant derived metabolites that inhibit cancer cells. This study aimed to evaluate the possible potency of the cucurbitacins for activation of AHR expression in CRC cell lines SW-480 and HT-29. The MTT assay was used to find the IC50 value of the metabolites in the cell lines. Afterwards, the cells were incubated with the IC50 concentrations of the cucurbitacins and AHR-mRNA expression assessed using RT-PCR. The IC50 values of CucD, CucE, and CucI were 4.5, 6.8, and 3.8 μM in HT-29 cell line and 35, 19, 17.5 μM in SW-480 cells, respectively. The SW-480 cells were more resistant against cucurbitacins in comparison with HT-29 cells and all three cucurbitacins led to more AHRmRNA expression in HT-29 cells. CucE had the lowest effect on AHR-mRNA expression in the cell lines and CucI was a common metabolite for both HT-29 and SW-480 cells, which showed the lowest IC50 value (the highest toxicity) and the highest effect on AHR-mRNA expression. CucI may have a potential AHR-induction role and it could be applicable as an AHR-expression inducer in CRC studies.
Researchers Abasalt Hosseinzadeh Colagar (Fifth Researcher), Zahra Khoshkam (Fourth Researcher), Mohammadreza Sheikhi (Third Researcher), Habib Zarredar (Second Researcher), Younes Aftabi (First Researcher)