Daucosterol disturbs redox homeostasis and elicits oxidative-stress mediated apoptosis in A549 cells via targeting thioredoxin reductase by a p53 dependent mechanism was written by Rajavel, Tamilselvam;Banu Priya, Gunasekeran;Suryanarayanan, Venkatesan;Singh, Sanjeev Kumar;Pandima Devi, Kasi. And the article was included in European Journal of Pharmacology in 2019.Computed Properties of C16H19BrN2OS The following contents are mentioned in the article:
Daucosterol (DS) is a plant phytosterol which is shown to induce oxidative stress mediated apoptosis in various cancer cell lines. However, the mol. mechanism underlying its cellular action has not been documented against Non- Small Cell Lung Cancer (NSCLC). Therefore, we attempted to decipher the mechanisms responsible for DS-induced anti-proliferation on human NSCLC cells. The present study showed, DS strongly inhibits the growth of A549 cells after 72 h time point with an IC50 value of ~20.9μM. Further DS elicits increased reactive oxygen species level and promote intrinsic apoptotic cell death on A549 cells as evidenced by increased expression of caspase-3, caspase-9, Bax, PARP inactivation, cytochrome-c release, and diminished expression of bcl-2 protein. DS failed to display its apoptotic actions upon pretreatment with the reactive oxygen species inhibitor NAC (N-acetyl cysteine). Indeed, apoptotic signal which was enhanced through p53/p21 activation and knockdown of p53 expression also moderately affected the DS induced apoptosis. In addition, DS preferentially inhibited the cell growth of p53 wild-type NSCLC cell lines than the mutant p53 models. Further, we show that inhibition of Thioredoxin (TrxR) redox system is principally associated with DS induced oxidative stress mediated apoptotic cell death on A549 cells. Moreover, we also demonstrated that DS stably interacted with serine residues in TrxR active sites. The obtained results confirmed that the anti-proliferative mechanism and increased reactive oxygen species level of DS was associated with down-regulation of TrxR1 pathway which triggers the p53 mediated intrinsic apoptotic mode of cell death in NSCLC cells. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Computed Properties of C16H19BrN2OS).
2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Computed Properties of C16H19BrN2OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica