Saeed Samarghandian - Medical Basic Science, Neyshabur University of Medical Sciences, Neyshabur, Iran
Tahere Farkhonde - Cardiovascular Diseases Research Center, Birjand University Medical of Science, Birjand, Iran

Background and Aim: Lung cancer has the highest mortality rate inthe world. Cancer chemotherapy can manage the progression of lungcancer and plants may have large contents of new antineoplastic agents.Thymoquinone (TQ) found in the plant Nigella has a potent anti-oxidantand anti-inflammatory activity. Objective: The purpose of the currentresearch was to evaluate the chemo-preventive action and relatedmechanisms of TQ against human lung cancer.Methods: The A549 cells were treated with the different concentrationsof TQ for the three following days. Cytotoxicity was tested throughMTT evaluation, production of necrosis and apoptosis by fluorescenceactivatedcell sorter analysis with propidium iodide (PI) and Annexin V,activation of caspase-3 and -9 by cleavage of specific substrates. DNAfragmentation through gel electrophoresis.Results: TQ inhibited proliferation in human tumor cell line and deathin the cells induced through apoptosis pathways. TQ also inhibited theapoptosis induced by the DNA fragmentation and activation of caspase-3and caspase-9. Treatment with TQ on lung cancer induced a significantelevation in Bax/Bcl2 ratios. Up-regulation of P53 by TQ showed theother pathway for inducing apoptosis in A549 cells. TQ caused apoptosiswhich is accompanied by the effect of caspases-3 and -9, acting asan upstream activator. Only recently patents of TQ derivatives for thetreatment of cancer are developed. This article also discusses our findingwith the patents for this agent.Conclusion: the current result may propose new pathways for theprevention and treatment of lung cancer through TQ for apoptosisinduction in A546 cells.

Anti-proliferative; A549 cells; Bax; Bcl2; Caspases; MTT; P53; Thymoquinone