title: Attenuation of natural killer cell functions by capsaicin through a direct and TRPV1-independent mechanism.
abstract: The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance.
authors.affiliation: Department of Biomedical Sciences, Department of Microbiology, Cellular Dysfunction Research Center and hunkim@amc.seoul.kr.
authors.forename: Hun Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences.
authors.forename: Hyung-Joon
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Sciences.
authors.forename: Gye Eun
authors.initials: GE
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Mi-Hyang
authors.initials: MH
authors.lastname: Cho
authors.affiliation: Cellular Dysfunction Research Center and Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Pain Cognitive Function Research Center, Dental Research Institute, Department of Neurobiology and Physiology, School of Dentistry and.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Davies
authors.affiliation: Pain Cognitive Function Research Center, Dental Research Institute, Department of Neurobiology and Physiology, School of Dentistry and, Department of Brain and Cognitive Sciences, College of Natural Sciences Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
authors.affiliation: Department of Microbiology.
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Microbiology.
authors.forename: Young Keol
authors.initials: YK
authors.lastname: Cho
authors.affiliation: Department of Microbiology, Cellular Dysfunction Research Center and.
authors.forename: Chul Hyun
authors.initials: CH
authors.lastname: Joo
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Seog Woon
authors.initials: SW
authors.lastname: Kwon
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Microbiology.
authors.forename: Yoo Kyum
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018689:Sensory System Agents / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin; D002118:Calcium