title: Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L.
abstract: In this study, the anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol (1) and lupeol (2), isolated from Diospyros lotus L., were explored. Compound 1 showed a marked concentration-dependent inhibition against 12-O-tetradecanoylphorbol-13-acetate (20 ng/32 pmol)-induced Epstein-Barr virus early antigen activation in Raji cells with IC50 of 270 μg/ml, without significant toxicity (70% viability). Compound 2 showed significant anti-tumour-promoting effect with IC50 of 412 μg/ml, without significant toxicity (60% viability). In heat-induced protein denaturation assay, compound 1 exhibited a concentration-dependent attenuation with a maximum effect of 73.5% at 500 μg/ml with EC50 of 117 μg/ml, while compound 2 exhibited a maximum effect of 59.2% at 500 μg/ml with EC50 of 355 μg/ml. Moreover, in silico docking studies against the phosphoinositide 3-kinase enzyme also show the inhibitory potency of these compounds. In short, both the compounds exhibited a marked anti-tumour-promoting and potent inhibitory effect on thermal-induced protein denaturation.
authors.affiliation: a Institute of Chemical Sciences, University of Peshawar , Peshawar 25120 , KPK , Pakistan.
authors.forename: Abdur
authors.initials: A
authors.lastname: Rauf
authors.affiliation: a Institute of Chemical Sciences, University of Peshawar , Peshawar 25120 , KPK , Pakistan.
authors.forename: Ghias
authors.initials: G
authors.lastname: Uddin
authors.affiliation: b Department of Pharmacy , Abdul Wali Khan University , Mardan 23200 , Pakistan.
authors.forename: Haroon
authors.initials: H
authors.lastname: Khan
authors.affiliation: a Institute of Chemical Sciences, University of Peshawar , Peshawar 25120 , KPK , Pakistan.
authors.forename: Muslim
authors.initials: M
authors.lastname: Raza
authors.affiliation: b Department of Pharmacy , Abdul Wali Khan University , Mardan 23200 , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zafar
authors.affiliation: c Department of Complementary and Alternative Medicine, Clinical R&D, Graduate School of Medical Science , Kanazawa University , 13-1 Takara-machi, Kanazawa 920-8640 , Japan.
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D029788:Diospyros / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D011489:Protein Denaturation / Q000187:drug effects; D012855:Sitosterols / Q000302:isolation & purification / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate; D000094042:Lupanes
chemical_list: D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D012855:Sitosterols; D013755:Tetradecanoylphorbol Acetate; C033305:Epstein-Barr virus early antigen; C025473:gamma-sitosterol; C010480:lupeol; D000094042:Lupanes
keywords: Diospyros lotus; anti-tumour-promoting and inhibitory activities of thermal-induced protein denaturation; docking studies against the phosphoinositide 3-kinase enzyme; lupeol; β-sitosterol