Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells

Breast cancer is heterogeneous and often hormone-dependent. There are many breast cancer treatment options, including endocrine therapy, chemotherapy, radiotherapy and targeted therapy. Unfortunately, not all patients respond to first-line treatments, and others will eventually relapse despite an initial response. Therapeutic options for these patients are limited. In the past decade, several studies have demonstrated the antitumor effect of celecoxib and luteolin in breast cancer as single treatment. The effect of combination treatment of celecoxib and luteolin in human breast cancer cells has not been well characterized. The present study examined the synergistic effect of celecoxib and luteolin on the human breast cancer cell lines MCF-7 and MDA-MB-231. We analyzed cell proliferation, cell death, apoptosis and changes in protein expression by performing cell survival assays, apoptosis assays and western blotting. The combination treatment significantly decreased cancer cell viability, and it had a greater efficiency in killing tumor cells after 72 h of treatment, compared to treatment with either agent alone or the control in a concentration- and time-dependent manner (P=0.01). The combination treatment demonstrated a greater than additive increase in breast cancer cell apoptosis (P=0.01). Decreased levels of Akt phosphorylation (pAkt) were noted after celecoxib and luteolin combination treatment. The combination of celecoxib and luteolin provided superior inhibition of breast cancer cell growth than either celecoxib or luteolin treatment alone. These results suggest that celecoxib and luteolin combination may be a new possible treatment option for breast cancer.