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


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.


CONCLUSIONS
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.
a Department of Pharmacology , School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran and.
Elham
E
Bakhtiari
b Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran.
Azar
A
Hosseini
a Department of Pharmacology , School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran and.|b Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran.
Mohammad Taher
MT
Boroushaki
a Department of Pharmacology , School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran and.|b Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences , Mashhad , Iran.
Seyed Hadi
SH
Mousavi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009570:Nitriles / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology*; D013450:Sulfones / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology*; D013777:Tetrazoles / Q000009:adverse effects / Q000819:agonists / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D047228:Angiotensin II Type 1 Receptor Blockers; D000970:Antineoplastic Agents; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D013777:Tetrazoles; C437965:olmesartan
Bay 11-7082; HeLa; cytotoxicity; olmesartan