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

Abstract:

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.

journal_name

Toxicol Mech Methods

authors

Bakhtiari E,Hosseini A,Boroushaki MT,Mousavi SH

doi

10.3109/15376516.2015.1053647

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

614-21

issue

8

eissn

1537-6516

issn

1537-6524

journal_volume

25

pub_type

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