title: Novel target genes responsive to apoptotic activity by Ocimum gratissimum in human osteosarcoma cells.
abstract: Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will metastasize to the lungs or liver, and as a result, patients generally need chemotherapy to improve survival possibility. Recently, antitumor activity has been reported in Ocimum gratissimum aqueous extract (OGE), which has been the focus of recent extensive studies on therapeutic strategies due to its antioxidant properties. We performed pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth. Cell viability, Western blot and flow cytometry analysis were performed before performing pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth, including cDNA microarray and RT-PCR assays. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of U2-OS and HOS cells. Increases in cell shrinkage, Sub-G1 fragments and the activation of caspase 3 indicated that OGE induced cell apoptosis in U2-OS and HOS cells. There was no change in human osteoblast hFOS cells. cDNA microarray assay demonstrated that the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers were all modified by OGE treatment. RT-PCR analysis also confirmed the down-regulation of SKA2 and BUB1B, and the up-regulation of PPP1R15A, SQSTM1, HSPA1B, and DDIT4 by OGE treatment. The finding of anticancer activity in OGE and the identification of some potential target genes raise the expectation that OGE may become a useful therapeutic drug for human OS.
authors.affiliation: Department of Materials Science and Engineering, National Chung Hsing University, Taichung, Taiwan , Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chao
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.forename: Jyuan-Jen
authors.initials: JJ
authors.lastname: Shu
authors.forename: Shiow-Kang
authors.initials: SK
authors.lastname: Yen
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D031339:Ocimum; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C584279:BUB1B protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C469991:DDIT4 protein, human; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D010936:Plant Extracts; C516428:SKA2 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1; D053148:Caspase 3