title: Competitive binding of (-)-epigallocatechin-3-gallate and 5-fluorouracil to human serum albumin: A fluorescence and circular dichroism study.
abstract: Combination therapy with more than one therapeutic agent can improve therapeutic efficiency and decrease drug resistance. In this study, the interactions of human serum albumin (HSA) with individual or combined anticancer drugs, (-)-epigallocatechin-3-gallate (EGCG) and 5-fluorouracil (FU), were investigated by fluorescence and circular dichroism (CD) spectroscopy. The results demonstrated that the interaction of EGCG or FU with HSA is a process of static quenching and EGCG formed a more stable complex. The competitive experiments of site markers suggested that both anti-carcinogens mainly bound to site I (subdomain IIA). The interaction forces which play important roles in the binding process were discussed based on enthalpy and entropy changes. Moreover, the competition binding model for a ternary system was proposed so as to precisely calculate the binding parameters. The results demonstrated that one drug decreased the binding affinity of another drug with HSA, resulting in the increasing free drug concentration at the action sites. CD studies indicated that there was an alteration in HSA secondary structure due to the binding of EGCG and FU. It can be concluded that the combination of EGCG with FU may enhance anticancer efficacy. This finding may provide a theoretical basis for clinical treatments.
authors: School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China.
authors: Lixia
authors: L
authors: Yuan
authors: School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China; Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China. Electronic address: panpanliumin@163.com.
authors: Min
authors: M
authors: Liu
authors: Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China.
authors: Guiqin
authors: G
authors: Liu
authors: Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China.
authors: Dacheng
authors: D
authors: Li
authors: Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China.
authors: Zhengping
authors: Z
authors: Wang
authors: Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China.
authors: Bingquan
authors: B
authors: Wang
authors: Institute of BioPharmceutical Research, Liaocheng University, Liaocheng 252059, China.
authors: Jun
authors: J
authors: Han
authors: School of Agriculture, Liaocheng University, Liaocheng 252059, China. Electronic address: zhangminliaoda@163.com.
authors: Min
authors: M
authors: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D002942:Circular Dichroism; D004357:Drug Synergism; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism; D017433:Protein Structure, Secondary; D000075462:Serum Albumin, Human / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014859:Warfarin / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014859:Warfarin; D002392:Catechin; C045651:epigallocatechin gallate; D005472:Fluorouracil; D007052:Ibuprofen; D000075462:Serum Albumin, Human
keywords: (−)-Epigallocatechin-3-gallate (EGCG); 5-Fluorouracil (FU); Circular dichroism (CD); Fluorescence quenching; Human serum albumin (HSA)