title: The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.
abstract: HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate < 0.05) that are dominantly involved in the cell cycle, apoptosis and adhesion-related biological signalling, including mitogen-activated protein kinase, focal adhesion and tight junction pathways, indicating the diverse effects of andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, Republic of China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Lai
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Wang
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D010946:Plants, Medicinal; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494650:DNAJB4 protein, human; D004224:Diterpenes; D050956:HSP40 Heat-Shock Proteins; C581727:JunB protein, human; D014157:Transcription Factors; C030419:andrographolide