title: 15,16-Dihydrotanshinone I-induced apoptosis in human colorectal cancer cells: involvement of ATF3.
abstract: 15,16-Dihydrotanshinone I (DHTS) is a component of the traditional Chinese medicinal plant Salvia miltiorrhiza Bunge. In this study, DHTS at as low as 2.5 μg/ml concentration significantly inhibited proliferation of human benign (SW480) and malignant (SW620) colorectal cancer cells, as shown by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometric analysis. Activating transcription factor (ATF)-3, a basic leucine zipper-type transcription factor, was found to be predominantly up-regulated in DHTS-treated SW480 and SW620 cells. The up-regulation of ATF3 was blocked by a c-JUN N-terminal kinase (JNK) or p38 inhibitor. Overexpression of ATF3 resulted in a significant augmentation of DHTS-induced apoptosis of SW480 cells, but resistance to DHTS-induced apoptosis of SW620 cells. These results suggest that DHTS has a strong therapeutic or preventive potential against cancer. In addition, ATF3 has a dual role in DHTS-induced apoptosis, depending on the degree of malignancy of colorectal cancer.
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 250 Wuxing St., Taipei 11031, Taiwan, ROC.
authors.forename: Fat-Moon
authors.initials: FM
authors.lastname: Suk
authors.forename: Wen-Ju
authors.initials: WJ
authors.lastname: Jou
authors.forename: Ren-Jye
authors.initials: RJ
authors.lastname: Lin
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Tzeng
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Liang
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D005663:Furans; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011809:Quinones
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D005663:Furans; D010616:Phenanthrenes; D011809:Quinones; C000713095:dihydrotanshinone I; D020928:Mitogen-Activated Protein Kinases
keywords: 15,16-Dihydrotanshinone I; SW420 cells; SW480; SW620; activating transcription factor-3; colorectal cancer