title: Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng.
abstract: Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The Km and Vmax values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC50 values were 16.00 μM and 9.83 μM, and Ki values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors.
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.|Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Jian
authors: J
authors: Xiao
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Dan
authors: D
authors: Chen
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Xiu-Xian
authors: XX
authors: Lin
authors: Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Shi-Fang
authors: SF
authors: Peng
authors: Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Mei-Fang
authors: MF
authors: Xiao
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Wei-Hua
authors: WH
authors: Huang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Yi-Cheng
authors: YC
authors: Wang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Jing-Bo
authors: JB
authors: Peng
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Dong-Sheng
authors: DS
authors: Ouyang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Yao
authors: Y
authors: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D011994:Recombinant Proteins; D013379:Substrate Specificity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D065729:Cytochrome P-450 CYP2C9; D065688:Cytochrome P-450 CYP2C9 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D036145:Ginsenosides; D011994:Recombinant Proteins; C112772:ginsenoside compound K