Inhibition of human cytochrome CYP1B1 by anthraquinone compounds,chrysophanol and physcion

The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.

Thermal Characterization and Decomposition Kinetics of Free Anthraquinones from Rhubarb

The thermal behaviour of aloe-emodin, chrysophanol and physcion and their kinetics have been investigated under non-isothermal conditions by means of differential thermal analysis （DTA） and thermogravimetry （TG）. The thermal characteristics have been determined using the DTA and TG-DTG curves. The non-isothermal kinetic data were analyzed by means of the Achar method and the Madhusudanan-Krishnan-Ninan （MKN） method. The possible reaction mechanisms have been investigated by comparing the kinetic parameters. The kinetic equation for aloe-emodin, chrysophanol and physcion can be expressed as dα/dt=Aexp（-E/RT）1/3（1-α）[-In（1-α]2. The activation energy E （kJ mol^-1） of the three free anthraquinones are 78.09, 89.54, and 107.5 and their InA/s^-1 are 22.98, 36.85 and 43.60, respectively.

Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis

BACKGROUND Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma(HCC).Physcion is a common bioactive anthraquinone that has potential as an anticancer agent.AIM To study the effect of physcion on sensitizing HCC cells to sorafenib.METHODS Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion.The cell viability,proliferation and apoptosis were measured by cell counting kit-8,colony formation,flow cytometry,and in vivo xenograft model.Glucose uptake,lactate acid production,extracellular acidification rate(ECAR),and oxygen consumption rate(OCR)were measured to analyze glycolysis.Expression of glycolysis-related regulators was assessed by western blotting.RESULTS The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells,manifested by enhanced apoptosis and suppressed cell growth.The glucose uptake,lactate acid production,and ECAR were elevated,and OCR was suppressed by physcion treatment.The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells,which was suppressed by physcion treatment.Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells.CONCLUSION Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.