ABSTRACT
BACKGROUND: Vitamin D is known for its anticancer potential. Prostaglandin E2 (PGE2) is a proliferative and inflammation-activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE2 metabolism was shown recently. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.
Subject(s)
Breast Neoplasms/pathology , Calcitriol/pharmacology , Celecoxib/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Vitamins/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Drug Therapy, Combination , Female , Humans , Tumor Cells, CulturedABSTRACT
BACKGROUND: Vitamin D is known for its anti-cancerogenous potential. Prostaglandin E2 (PGE2) is a proliferation and inflammation activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX-2). A link between vitamin D and PGE2 metabolism was recently shown. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines we investigated the influence of calcitriol and the COX-2 inhibitor celecoxib regarding cell growth via MTT test, as well as on the protein and mRNA expression of COX-2 using western blot and qRT-PCR. RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX-2 inhibitor celecoxib and even stronger by their combination. Moreover, calcitriol inhibited the COX-2 protein expression in MDA-MB-231, as well as the COX-2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a cooperative growth-inhibiting effect in breast cancer cell lines.
Subject(s)
Breast Neoplasms/drug therapy , Cyclooxygenase 2 Inhibitors/therapeutic use , Vitamin D/therapeutic use , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Cell Line, Tumor , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Female , HumansABSTRACT
BACKGROUND: Vitamin D exhibits multiple anti-proliferative and pro-differentiating actions. Prostaglandin-(PG)E2 is a tumor-promoting tissue hormone anabolized by cyclooxygenase-2 (COX-2). Recently, a link between the PG and vitamin D metabolism was reported. MATERIALS AND METHODS: The influence of calcitriol and celecoxib on the proliferation of ovarian cancer cell lines was measured and the impact of calcitriol on the protein and mRNA expression of COX-2 was quantified by western blot and qRT-PCR, respectively. RESULTS: After COX-2 induction with interleukin (IL)-1ß, 10 µM celecoxib did not significantly inhibit the proliferation of OVCAR-3 cells, whereas calcitriol showed such an effect; however, the combination of the two substances had an additive influence. After induction by IL-1ß, calcitriol inhibited the COX-2 protein, as well as its mRNA expression significantly in OVCAR-3 and SKOV-3 cells. CONCLUSION: These data suggest a correlation between PG and vitamin D metabolism in their anti-tumorigenic activity in ovarian carcinomas.
