Sulforaphane combats colon cancer in vitro by inhibiting COX-2 and prostaglandin E1 synthase and exhibiting anti-angiogenic, anti-proliferative, and anti-metastatic properties.

PMID: 

Cells Tissues Organs. 2018 ;206(1-2):46-53. Epub 2018 Jul 24. PMID: 30041241

Abstract Title: 

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells.

Abstract: 

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.

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