title: 12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis.
abstract: (20R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12β-O-(L-Chloracetyl)-dammar-20(22)-ene-3β,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xu De
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Fan Zhi
authors.initials: FZ
authors.lastname: Qu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: zyq4885@126.com.
authors.forename: Yu Qing
authors.initials: YQ
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005894:Panax / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097669:Dammaranes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D014315:Triterpenes; D000097669:Dammaranes; C000618493:12beta-O-(L-chloracetyl)-dammar-20(22)-ene-3beta,25-diol
keywords: 12-Chloracetyl-PPD; 25-OH-PPD; Apoptosis; Cell cycle; Reactive oxygen species