PMID- 30041241 OWN - NLM STAT- MEDLINE DCOM- 20190919 LR - 20211204 IS - 1422-6421 (Electronic) IS - 1422-6405 (Linking) VI - 206 IP - 1-2 DP - 2018 TI - Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells. PG - 46-53 LID - 10.1159/000490394 [doi] AB - BACKGROUND: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents. METHODS: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test. RESULTS: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells. CONCLUSIONS: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis. CI - (c) 2018 S. Karger AG, Basel. FAU - Tafakh, Maryam Sadat AU - Tafakh MS AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Saidijam, Massoud AU - Saidijam M AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Ranjbarnejad, Tayebeh AU - Ranjbarnejad T AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Malih, Sara AU - Malih S AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Mirzamohammadi, Solmaz AU - Mirzamohammadi S AD - Department of Pharmacology, Shahroud University of Medical Sciences, Sharoud, Iran. FAU - Najafi, Rezvan AU - Najafi R AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran, najafi2535@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180724 PL - Switzerland TA - Cells Tissues Organs JT - Cells, tissues, organs JID - 100883360 RN - 0 (Anticarcinogenic Agents) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Isothiocyanates) RN - 0 (Sulfoxides) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 5.3.99.3 (PTGES protein, human) RN - EC 5.3.99.3 (Prostaglandin-E Synthases) RN - GA49J4310U (sulforaphane) SB - IM MH - Anticarcinogenic Agents/*pharmacology MH - Cell Survival/drug effects MH - Colonic Neoplasms/*drug therapy/genetics/metabolism/prevention & control MH - Cyclooxygenase 2/metabolism MH - Cyclooxygenase 2 Inhibitors/*pharmacology MH - Down-Regulation/drug effects MH - Gene Expression Regulation, Neoplastic/*drug effects MH - HT29 Cells MH - Humans MH - Isothiocyanates/*pharmacology MH - Prostaglandin-E Synthases/*antagonists & inhibitors/genetics MH - Sulfoxides OTO - NOTNLM OT - Colorectal cancer OT - Cyclooxygenase-2 OT - Microsomal prostaglandin E synthase-1 OT - Prostaglandin E2 OT - Sulforaphane EDAT- 2018/07/25 06:00 MHDA- 2019/09/20 06:00 CRDT- 2018/07/25 06:00 PHST- 2017/09/24 00:00 [received] PHST- 2018/05/25 00:00 [accepted] PHST- 2018/07/25 06:00 [pubmed] PHST- 2019/09/20 06:00 [medline] PHST- 2018/07/25 06:00 [entrez] AID - 000490394 [pii] AID - 10.1159/000490394 [doi] PST - ppublish SO - Cells Tissues Organs. 2018;206(1-2):46-53. doi: 10.1159/000490394. Epub 2018 Jul 24.