title: Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway.
abstract: Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data foster hope for novel nutrition based combination therapies in SCLC.
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Friedman
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Haley E
authors.initials: HE
authors.lastname: Perry
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Brown
authors.affiliation: Department of Biology, Alderson Broaddus University, Philippi, WV 26416, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Biology, Alderson Broaddus University, Philippi, WV 26416, United States.
authors.forename: Ju
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Cathyrn D
authors.initials: CD
authors.lastname: Stevenson
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: John D
authors.initials: JD
authors.lastname: Hurley
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Nolan
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Austin T
authors.initials: AT
authors.lastname: Akers
authors.affiliation: Department of Biology, Alderson Broaddus University, Philippi, WV 26416, United States.
authors.forename: Yi Charlie
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Denning
authors.affiliation: Department of Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Brown
authors.affiliation: Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States. Electronic address: dasgupta@marshall.edu.
authors.forename: Piyali
authors.initials: P
authors.lastname: Dasgupta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002645:Chickens; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D002154:Calpain; D002211:Capsaicin; D002166:Camptothecin
keywords: Apoptosis; Calpain; Camptothecin; Capsaicin; Small cell lung cancer (SCLC)