AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colo...AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(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 Lo Vo 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.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, 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 LoV o 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 LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.展开更多
基金Supported by (in part) the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence,No.MOHW105-TDU-B-212-133019
文摘AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(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 Lo Vo 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.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, 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 LoV o 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 LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
