title: (3S)-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid from Cichorium endivia. L induces apoptosis of human colorectal cancer HCT-8 cells.
abstract: Cichorium endivia. L, consumed either cooked or eaten raw in salads, is a popular kind of vegetable cultivated all around the World. Its components have been widely used in folk medicine in anti-inflammatory therapy. However, the anti-cancer activity of the components has never been reported. In this study, (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1), an amino acid isolated from C. endivia. L, was found for the first time to show cytotoxic activity in colorectal cancer cell line HCT-8. Compound 1 at concentrations of 0.5-4 μM induced apoptosis of HCT-8 cells in a dose-dependent manner. The compound 1-induced apoptosis in HCT-8 cells was accompanied by the loss of mitochondrial membrane potential, the activation of caspase-3, caspase-8 and caspase-9, the up-regulation of Bax and the down-regulation of Bcl-2. In addition, compound 1 suppressed the activation of NF-κB, which acts as an inhibitor of apoptosis. Taken together, these results suggested that compound 1 could significantly induce apoptosis of HCT-8 cells through the suppression of NF-κB signaling pathway, and thus can be considered as a potential candidate for developing chemotherapeutic drugs against cancer.
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China.
authors.forename: Fu-Xin
authors.initials: FX
authors.lastname: Wang
authors.forename: An-Jun
authors.initials: AJ
authors.lastname: Deng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Wei
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Qin
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D015153:Blotting, Western; D002243:Carbolines / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D002243:Carbolines; D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C054910:1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9