Interaction of saffron carotenoids with catalase: in vitro, in vivo and molecular docking studies

Abstract The effects of saffron carotenoids, crocetin (Crt) and crocin (Cro) on the structure, function and kinetics of catalase (CAT) were investigated. Both Crt and Cro quenched the fluorescence emission of CAT through the dynamic mechanism, but Crt (Ksv= 8.1 × 104 mol−1) was more effective than Cro (Ksv= 0.6 × 104 mol−1) at 300 °K. The UV–vis and circular dichroism spectra showed conformational changes of CAT in the presence of both carotenoids, but with different degrees. Kinetic studies showed strong inhibition of CAT by Crt, while, different concentrations of Cro showed different effects. Our in vitro data showed that Crt treatment significantly (p = 0.002) reduced the CAT activity in MCF-7, up to 24 h. The in vivo results showed that both Crt and Cro significantly increased the CAT activity in the tumor (p = 0.000 for both), and liver (p = 0.000 and p = 0.026 for Crt and Cro, respectively) tissues of 4T1-induced breast cancer in BALB/c mice, after 4 weeks of treatment. These findings are consistent with the binding, thermodynamic and molecular docking data. In conclusion, Crt and Cro with some differences in the structure affect CAT structure, function and activity, but in a slightly different manner. Communicated by Ramaswamy H. Sarma

[1]  Jianbo Xiao,et al.  Stereoselective interactions of lactic acid enantiomers with HSA: Spectroscopy and docking application. , 2019, Food chemistry.

[2]  S. Z. Bathaie,et al.  Evaluating the cytotoxic effect of crocin on MDA-MB-468 cell line based on apoptosis induction, ER stress, and autophagy markers , 2018 .

[3]  S. Z. Bathaie,et al.  Saffron carotenoids (crocin and crocetin) binding to human serum albumin as investigated by different spectroscopic methods and molecular docking , 2018, Journal of biomolecular structure & dynamics.

[4]  Jing Zhang,et al.  Interaction of chromium(III) or chromium(VI) with catalase and its effect on the structure and function of catalase: An in vitro study. , 2018, Food chemistry.

[5]  A. Sahebkar,et al.  Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  Zhiming Ge,et al.  Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat model. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[7]  Guangji Wang,et al.  Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats. , 2017, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[8]  H. Zhang,et al.  Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice , 2016, Biomolecules & therapeutics.

[9]  S. Z. Bathaie,et al.  Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract , 2016, Molecules.

[10]  E. Altinoz,et al.  Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats. , 2016, General physiology and biophysics.

[11]  AshrafiMahboobeh,et al.  Effect of Crocin on Cell Cycle Regulators in N-Nitroso-N-Methylurea-Induced Breast Cancer in Rats. , 2015 .

[12]  Yun Qi,et al.  Neuroprotective Effects of Crocin against Oxidative Stress Induced by Ischemia/Reperfusion Injury in Rat Retina , 2015, Ophthalmic Research.

[13]  S. C. Kim,et al.  Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines. , 2014, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[14]  H. Hara,et al.  Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice. , 2013, European journal of pharmacology.

[15]  S. Z. Bathaie,et al.  Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. , 2013, DNA and cell biology.

[16]  Hesham A El-Beshbishy,et al.  Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. , 2012, Ecotoxicology and environmental safety.

[17]  G. Bauer.  Tumor cell-protective catalase as a novel target for rational therapeutic approaches based on specific intercellular ROS signaling. , 2012, Anticancer research.

[18]  Uttam Anand,et al.  Deciphering the role of pH in the binding of ciprofloxacin hydrochloride to bovine serum albumin. , 2012, Physical chemistry chemical physics : PCCP.

[19]  Caroline Louis-Jeune,et al.  Prediction of protein secondary structure from circular dichroism using theoretically derived spectra , 2012, Proteins.

[20]  T. Ishrat,et al.  Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment , 2012, Neurological Sciences.

[21]  S. Mousavi,et al.  Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form , 2011, Pharmaceutical biology.

[22]  Lorenzo Stella,et al.  Fluorescence quenching and ligand binding: A critical discussion of a popular methodology , 2011 .

[23]  Rutao Liu,et al.  Potential enzyme toxicity of oxytetracycline to catalase. , 2010, The Science of the total environment.

[24]  S. M. Asdaq,et al.  Potential of Crocus sativus (saffron) and its Constituent, Crocin, as Hypolipidemic and Antioxidant in Rats , 2010, Applied biochemistry and biotechnology.

[25]  G. Bauer,et al.  Multiple protective functions of catalase against intercellular apoptosis-inducing ROS signaling of human tumor cells , 2010, Biological chemistry.

[26]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[27]  H. Bakshi,et al.  DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. , 2010, Asian Pacific journal of cancer prevention : APJCP.

[28]  S. Mousavi,et al.  Protective Effect of Saffron Extract and Crocin on Reactive Oxygen Species-Mediated High Glucose-Induced Toxicity in PC12 Cells , 2010, Cellular and Molecular Neurobiology.

[29]  G. Bauer,et al.  Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling. , 2009, Anticancer research.

[30]  G. Bauer,et al.  Modulation of intercellular ROS signaling of human tumor cells. , 2009, Anticancer research.

[31]  Y. Liu,et al.  Antioxidant potential of crocins and ethanol extracts of Gardenia jasminoides ELLIS and Crocus sativus L.: A relationship investigation between antioxidant activity and crocin contents , 2008 .

[32]  Z. Qian,et al.  Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats. , 2007, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[33]  Chong-Zhi Wang,et al.  Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. , 2007, Experimental oncology.

[34]  D. Sakthisekaran,et al.  Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies , 2006, Molecular and Cellular Biochemistry.

[35]  G. Bauer,et al.  Differential role of extra- and intracellular superoxide anions for nitric oxide-mediated apoptosis induction. , 2004, In vivo.

[36]  V. Ilyukha.  Superoxide Dismutase and Catalase in the Organs of Mammals of Different Ecogenesis , 2001, Journal of Evolutionary Biochemistry and Physiology.

[37]  G. Bauer,et al.  Nitric oxide mediates apoptosis induction selectively in transformed fibroblasts compared to nontransformed fibroblasts. , 2002, Carcinogenesis.

[38]  G. Bauer,et al.  Target cell-derived superoxide anions cause efficiency and selectivity of intercellular induction of apoptosis. , 2000, Free radical biology & medicine.

[39]  J. Tainer,et al.  Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. , 2000, Journal of molecular biology.

[40]  Y. L. Lin,et al.  Inhibitory effect of crocetin on benzo(a)pyrene genotoxicity and neoplastic transformation in C3H10T1/2 cells. , 1996, Anticancer research.

[41]  M. Nikiforov,et al.  Mechanisms of unusually high antioxidant activity of RSV‐SR‐transformed cells and of its suppression by activated p21ras , 1996 .

[42]  G. Alonso,et al.  Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. , 1996, Cancer letters.

[43]  C. Wang,et al.  Effects of crocetin on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. , 1991, Carcinogenesis.

[44]  Deĭchman Gi,et al.  Sensitivity to hydrogen peroxide and in vivo survival of Syrian hamster cells transformed in vitro with Rous sarcoma virus , 1987 .

[45]  William R. Ware,et al.  OXYGEN QUENCHING OF FLUORESCENCE IN SOLUTION: AN EXPERIMENTAL STUDY OF THE DIFFUSION PROCESS , 1962 .