title: Non-pungent long chain capsaicin-analogs arvanil and olvanil display better anti-invasive activity than capsaicin in human small cell lung cancers.
abstract: The nutritional compound capsaicin inhibits the invasion of many types of human cancers. The clinical development of capsaicin as an anti-cancer drug is limited due to its unfavorable side effects like burning sensation, stomach cramps, gut pain and nausea. This study compared the anti-invasive activity of capsaicin to non-pungent long chain capsaicin analogs, namely arvanil and olvanil, in human small cell lung cancer cells. Boyden chamber invasion assays revealed that arvanil and olvanil displayed improved anti-invasive activity relative to capsaicin in human SCLC cells. The results of the Boyden chamber assay were confirmed by the spherical invasion assay, and similar results were obtained. The anti-invasive activity of arvanil, olvanil and capsaicin were independent of TRPV and CB1 receptors. Furthermore, the anti-invasive activity of arvanil, olvanil and capsaicin was mediated by the AMPK pathway. Depletion of AMPK levels by siRNA methodology abrogated the anti-invasive activity of arvanil, olvanil and capsaicin. The non-pungent capsaicin analogs arvanil and olvanil display improved anti-invasive activity relative to capsaicin in human SCLC cells. These agents may represent the second generation of capsaicin-like compounds which are more potent than the parent molecule and have a better side effect profile.
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Hurley
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: Austin T
authors.initials: AT
authors.lastname: Akers
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Friedman
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Nolan
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Brown
authors.affiliation: a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
authors.forename: Piyali
authors.initials: P
authors.lastname: Dasgupta
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D055752:Small Cell Lung Carcinoma / Q000473:pathology*; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C121153:arvanil; C054256:olvanil; D000263:Adenylate Kinase; D002211:Capsaicin
keywords: AMPK; SCLC; arvanil; capsaicin; invasion; olvanil