title: Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.
abstract: Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Pawel T
authors.initials: PT
authors.lastname: Szymanski
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Bhimanna
authors.initials: B
authors.lastname: Kuppast
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: College of Pharmacy, Qatar University, Doha 02713, Qatar.
authors.forename: Sherief
authors.initials: S
authors.lastname: Khalifa
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Hesham
authors.initials: H
authors.lastname: Fahmy
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000517:prevention & control*
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C573078:sarcophine-diol; C014804:sarcophine; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D020169:Caspases; D015107:4-Butyrolactone