title: Effective melanoma inhibition by synthetic pentacyclic triterpenoid 2-(3-phenylprop-2-en-1-ylidene)-22β-hydroxy-3-oxoolean-12-en-28-oic acid: an in vitro and in vivo study.
abstract: The C-2 arylidene analog (compound 3) of pentacyclic triterpenoid Lantadene A (compound 1) was synthesized and evaluated by the National Cancer Institute, USA, for in vitro cytotoxicity against a panel of melanoma cancer cell lines: LOX IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-2, SK-MEL-28, SK-MEL-5, UACC-257 UACC-62 and B16F10. Compound 3 showed enhanced cytotoxicity compared with compound 1 and the standard drug cisplatin. At the same time, compound 3 showed selective toxicity toward cancer cells and was inactive (i.e., nontoxic) against normal cells (VERO). Compound 3 induced sub-G1 cell cycle arrest and apoptosis in B16F10 cells by down-regulating NF-κB, c-jun, Bcl-2, and by activating caspase-3 and Bax expression. Compound 3 also demonstrated beneficial effects in a clinically relevant B16F10 allograft mice model, with significant reduction of tumor growth/tumor weight in vivo. Compound 3 improved the survival rate in comparison to the control group and the cisplatin group. At the same time, compound 3 had a better safety profile than cisplatin in terms of hematological parameters and liver enzyme levels.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat 173234 India.
authors.forename: Navin Kumar
authors.initials: NK
authors.lastname: Tailor
authors.forename: Hong Boon
authors.initials: HB
authors.lastname: Lee
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D053978:Pentacyclic Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014184:Transplantation, Homologous; D014709:Vero Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; D009828:Oleanolic Acid; C019074:rehmannic acid; D053148:Caspase 3