(3S)-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic Acid from Cichorium endivia. L Induces Apoptosis of Human Colorectal Cancer HCT-8 Cells
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
State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China
Department of Microecology, Dalian Medical University, No.9 Western Section, Lvshun South Street, Lvshunkou District, 116044, Dalian, China
Authors to whom correspondence should be addressed.
Molecules 2013, 18(1), 418-429; https://doi.org/10.3390/molecules18010418
Received: 19 November 2012 / Revised: 13 December 2012 / Accepted: 17 December 2012 / Published: 28 December 2012
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.