title: Antineoplastic Effects of Honokiol on Melanoma.
abstract: Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma.
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Guillermo-Lagae
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA; Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute (RPCI), Buffalo, NY 14263, USA.
authors.forename: Sreevidya
authors.initials: S
authors.lastname: Santha
authors.affiliation: Department of Biology and Microbiology; and Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA; University of Maryland Baltimore Washington Medical Center, Glen Burnie, MD 21061, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Zoelle
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Department of Biology and Microbiology; and Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Radhey S
authors.identifier: 0000-0003-4204-9323
authors.initials: RS
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Chandradhar
authors.identifier: 0000-0003-3478-8660
authors.initials: C
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D017705:Lignans; D009363:Neoplasm Proteins; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols