title: Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo.
abstract: Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca(2+) together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy.
authors.affiliation: Experimental Oncology Unit (UNONEX), Federal University of São Paulo, SP, Brazil. Electronic address: nataliagirola@hotmail.com.
authors.forename: Natalia
authors.initials: N
authors.lastname: Girola
authors.affiliation: Experimental Oncology Unit (UNONEX), Federal University of São Paulo, SP, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Figueiredo
authors.affiliation: Experimental Oncology Unit (UNONEX), Federal University of São Paulo, SP, Brazil.
authors.forename: Camyla F
authors.initials: CF
authors.lastname: Farias
authors.affiliation: Laboratory of Tumor Immunology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Azevedo
authors.affiliation: Laboratory of Tumor Immunology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
authors.forename: Adilson K
authors.initials: AK
authors.lastname: Ferreira
authors.affiliation: Laboratory of Tumor Immunology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Teixeira
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, SP, Brazil.
authors.forename: Tabata M
authors.initials: TM
authors.lastname: Capello
authors.affiliation: Institute of Biosciences, University of São Paulo, SP, Brazil.
authors.forename: Euder G A
authors.initials: EG
authors.lastname: Martins
authors.affiliation: Interdepartmental Group of Health Economics (Grides), Federal University of São Paulo, SP, Brazil.
authors.forename: Alisson L
authors.initials: AL
authors.lastname: Matsuo
authors.affiliation: Experimental Oncology Unit (UNONEX), Federal University of São Paulo, SP, Brazil.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, SP, Brazil.
authors.forename: João H G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000081008:Bicyclic Monoterpenes; D002118:Calcium / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D031701:Piper / Q000737:chemistry*; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000081008:Bicyclic Monoterpenes; D037282:Calreticulin; D013729:Terpenes; C019286:camphene; D002118:Calcium
keywords: Antitumor; Apoptosis; Camphene; Melanoma