Bisdemethoxycurcumin alleviates vandetanib-induced cutaneous toxicity in vivo and in vitro through autophagy activation was written by Jin, Ying;Chen, Xueqin;Gao, Zizheng;Shen, Xiaofei;Fu, Huangxi;Pan, Zezheng;Yan, Hao;Yang, Bo;He, Qiaojun;Xu, Zhifei;Luo, Peihua. And the article was included in Biomedicine & Pharmacotherapy in 2021.Application of 33171-05-0 The following contents are mentioned in the article:
High incidence of cutaneous toxicity ranging from 29.2% to 71.2% has been reported during clin. use of vandetanib, which is a multi-target kinase inhibitor indicated for the treatment of unresectable medullary thyroid carcinoma. The cutaneous toxicity of vandetanib has limited its clin. benefits, but the underlying mechanisms and protective strategies are not well studied. Hence, we firstly established an in vivo model by continuously administrating vandetanib at 55 mg/kg/day to C57BL/6 for 21 days and verified that vandetanib could induce skin rash in vivo, which was consistent with the clin. study. We further cultured HaCaT and NHEK cells, the immortalized or primary human keratinocyte line, and investigated vandetanib (0-10μM, 0-24 h)-caused alteration in cellular survival and death processes. The western blot showed that the expression level of apoptotic-related protein, c-PARP, c-Caspase 3 and Bax were increased, while the anti-apoptotic protein Bcl2 and MCL1 level were decreased. Meanwhile, vandetanib downregulated mitochondrial membrane potential which in turn caused the release of Cytochrome C, excessive production of reactive oxygen species and DNA damage. Furthermore, we found that 5μM bisdemethoxycurcumin partially rescued vandetanib-induced mitochondria pathway-dependent keratinocyte apoptosis via activation of autophagy in vivo and in vitro, thereby ameliorated cutaneous toxicity. Conclusively, our study revealed the mechanisms of vandetanib-induced apoptosis in keratinocytes during the occurrence of cutaneous toxicity, and suggested bisdemethoxycurcumin as a potential protective drug. This work provided a potentially promising therapeutic strategy for the treatment of vandetanib-induced cutaneous toxicity. This study involved multiple reactions and reactants, such as Bisdemethoxycurcumin (cas: 33171-05-0Application of 33171-05-0).
Bisdemethoxycurcumin (cas: 33171-05-0) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Application of 33171-05-0
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem