Synergistic, cytotoxic and apoptotic activities of olmesartan with NF-κB inhibitor against HeLa human cell line

Context: Over expression of renin-angiotensin system (Ras) and nuclear factor-kappaB (NF-κB) has a major role in many cancers. It has been suggested that some Angiotensin Receptor blockers (ARBs) could reduce the proliferation of Cancer cells. The role of NF-κB pathway has been documented in cell proliferation.

Objective: In this study, the role of angiotensin II and NF-κB pathway in human cervical Cancer cell line (HeLa) proliferation was studied using olmesartan (as a novel Ag II antagonist) and Bay11-7082 (as NF-κB Inhibitor).

Materials and methods: HeLa cells were treated with different concentrations of olmesartan and Bay11-7082. Cell proliferation was determined after 24, 48, and 72 h by MTT assay. Synergistic activity of olmesartan with Bay11-7082 was analyzed with Compusyn software. Apoptotic cells were determined using PI staining of DNA fragmentation.

Results: Cell viability decreased with olmesartan and Bay11-7082 in HeLa cells by 24, 48 and 72 h. Olmesartan had synergistic activity with Bay11-7082 and combinations of olmesartan with Bay11-7082 decreased cell viability as compared with single agent treatments. Olmesartan and Bay11-7082 induced a sub-G1 peak in flow cytometry histogram of treated cells indicating that apoptotic cell death is involved in olmesartan and Bay11-7082-induced toxicity.

Discussion and conclusion: Results imply that olmesartan and Bay11-7082 inhibit the growth of HeLa cells as a concentration- and time-dependent mode and they have synergistic activity. Results show that Ras and NF-κB pathway blockade lead to significant cytotoxicity against tumor cell line. So, ARBs and NF-κB pathway inhibitors could be considered as good anti-cancer agents in cervix carcinoma after further studies.