China
Africa
Explore chapters and articles related to this topic
Recent Advancements of Curcumin Analogs and Curcumin Formulations in Context to Modern Pharmacotherapeutics Perspectives
Published in Debarshi Kar Mahapatra, Cristóbal Noé Aguilar, A. K. Haghi, Applied Pharmaceutical Practice and Nutraceuticals, 2021
Animeshchandra G. M. Haldar, Kanhaiya M. Dadure, Debarshi Kar Mahapatra
Curcumin has an important property as a binding inhibitor of CBR1, was first reported by Hintz Peter et al.52 Curcumin worked as a cofactor by blocking the CBR1 binding sites that affect daunorubicinol formation. Curcumin can leave the potential to enhance the efficiency of daunorubicin through the inhibition of CBR1 mediated reduction of daunorubicin to daunorubicinol. The inhibitory action of CBR1 can enhance the efficiency of daunorubicin in cancer tissue.
Role of Genetic Variability in Breast Cancer Treatment Outcomes
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
Kandace L. Amend, Ji-Yeob Choi, Christine B. Ambrosone
Carbonyl reductase (CBR) is a monomeric, NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of carbonyl compounds, including doxorubicin and daunorubicin. In humans, two CBRs have been identified, CBR1 and CBR3. An SNP has been identified in CBR3 (CBR3 V244M), where the M244 isoform results in higher Vmax and is 100% more efficient in catalyzing the reduction of substrate (39). To our knowledge, CBRs have not been investigated in relation to breast cancer outcomes following treatment with anthracyclines.
Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression
Published in Pharmaceutical Biology, 2022
Yuan Lu, Wen Liu, Ting Lv, Yanli Wang, Ting Liu, Yi Chen, Yang Jin, Jin Huang, Lin Zheng, Yong Huang, Yan He, Yongjun Li
H9c2 cells were incubated with ADI (10%) or an equivalent volume of PBS for 18 h. Subsequently, protein samples were extracted from cellular lysate. Protein concentration was quantified by BCA assay, then measured by absorption in a spectrophotometer. After that, CBR1 protein was assessed by western blot as described (Endo et al. 2021). Briefly, the protein was separated by SDS-polyacrylamide gel electrophoresis and transferred to a polyvinylidene fluoride transfer membrane (PVDF, Millipore, Bedford, MA, USA). The membranes were blocked with 5% skimmed milk for 1 h at room temperature and then incubated with the corresponding primary antibodies against CBR1 (1:1000) and GADPH (1:5000) overnight at 4 °C. The membrane was then incubated with horseradish peroxidase-conjugated secondary antibody for 2 h at room temperature. After washing with TBST 3 times (5 min each), the membranes were photographed using a gel imager (Thermo Fisher Scientific). All the target proteins were normalised by GADPH and calculated as the percentage of the control.
Differential changes in the pharmacokinetics of doxorubicin in diethylnitrosamine-induced hepatocarcinoma model rats
Published in Xenobiotica, 2020
Jie Pan, Yuan Lu, Shuai Zhang, Yueting Li, Jia Sun, Hua Chunhua Liu, Zipeng Gong, Jing Huang, Chuang Cao, Yonglin Wang, Yongjun Li, Ting Liu
Previous studies of DOX metabolism were based on the metabolism in liver. Half of DOX is eliminated from the body in the original form. The formation of DOX is mainly mediated via carbonyl reductases. CBRs include three isoformsin: CBR1, CBR3 and CBR4. Among them, CBR1 has been a most important pathway which contributes to the metabolism of DOX (Wang et al., 2019). Due to its broad substrate specificity, rat cbr1 is involved in metabolizing a number of clinically important drugs (Shi & Di, 2017). Moreover, cbr1 is an NADPH-dependent oxidoreductase that reduces DOX to doxorubicinol (Jo et al., 2017). In the present study, the protein expression of cbr1 was investigated. The results showed that down-regulated expression of cbr1 in HCC rats may be important, and can lead to high blood concentrations of DOX in HCC rats.
Nucleoside diphosphate kinase 2 confers acquired 5-fluorouracil resistance in colorectal cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Shaojia Wen, Xun Wang, Yamin Wang, Jianfeng Shen, Junyi Pu, Hui Liang, Chao Chen, Linna Liu, Penggao Dai
Among the regulated genes, the methylation of CBR1, UGT2A1 and RFC3 were all downregulated (β difference >0.3), indicating that these genes might involve in 5-FU chemoresistance to in CRC. Carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase superfamily, catalyses the reduction of the ketone, aldehyde and C=C bond of ONE into 4-hydroxy-2-nonenal (HNE), 4-oxo-2-nonenol and 4-oxononanal, respectively [32]. This gene has been reported to mediate DOX reduction and suggested to develop the chemoresistance in cancer cells [33]. UGT2A1 belongs to UDP-glycosyltransferase family, which catalyse biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds, UGT2A1 exhibited highest expression in the lung, colon and liver and other tissues [34], hence, it may play an important role in drug resistance. RFC3 mainly functioned in DNA replication, nucleotide excision repair and mismatch repair. It may affect the efficacy of drugs similar to paclitaxel’s and it also reported to over-expressed in many kinds of cancers. When RFC3 gene was silenced, ovarian tumour cells proliferation were greatly suppressed [35].