Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

Abstract

AIMTo identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODSOur experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.RESULTSOur results showed that 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSIONTQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.

Prostaglandin EP2 receptor: Novel therapeutic target for human cancers (Review)

“…The function of the EP2 receptor. Numerous studies have demonstrated that EP2 is abnormally expressed in cancer, including colon, prostate, liver and breast cancer (5,(40)(41)(42)(43) (Fig. 4).…”

Cryptotanshinone (Dsh‐003) from Salvia miltiorrhiza Bunge inhibits prostaglandin E2‐induced survival and invasion effects in HA22T hepatocellular carcinoma cells

“…35 PGE2 is involved in the β-catenin pathway and therefore accelerates the progression of cancers of breast, neuroblastoma, hepatocellular carcinoma, and colorectal cancer. [44][45][46][47][48] β-catenin is an important player in the Wnt signaling pathway and its nuclear translocation results in regulating the expression of various target genes associated cellular processes such as cell survival, proliferation, and migration. 49,50 Our present study revealed that Dsh-003 could block PGE2-induced cell migration effect, finally, and reversed PGE2 induced β-catenin signaling pathway.…”

Thymoquinone inhibits metastatic phenotype and epithelial‑mesenchymal transition in renal cell carcinoma by regulating the LKB1/AMPK signaling pathway

“…Thymoquinone (TQ), isolated from the seeds of Nigella sativa, is a natural polyphenolic compound (3). Numerous studies have reported that TQ has broad pharmacological effects.…”