title: Furano-1,2-Naphthoquinone Inhibits Src and PI3K/Akt Signaling Pathways in Ca9-22 Human Oral Squamous Carcinoma Cells.
abstract: Furano-1,2-naphthoquinone (FNQ), a biologically active component ofAvicennia marina, has been demonstrated to display anticancer activity. FNQ exerted cytotoxicity with the G2/M cell cycle arrest and apoptosis in Ca9-22 cells. FNQ-induced G2/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin-dependent kinases (CDK) 1 and 2 with concomitant induction of p27. FNQ-induced apoptosis was accompanied by Bax and Bad upregulation, and the downregulation of Bcl-2, Bcl-XL, Mcl-1, and X-linked inhibitor of apoptosis (XIAP), resulting in cytochrome C release and sequential activation of caspase-9 and caspase-3. Mechanistic studies showed that FNQ suppressed Src phosphorylation, PI3K, and Akt activation in Ca9-22 cells. Moreover, the Src inhibitor PP2 reduced the phosphorylation of Src and activation of PI3K/Akt, which was comparable with FNQ treatment. The combined treatment of FNQ with PP2 enhanced the cell cycle arrest and apoptosis and also led to the downregulation of Bcl-XL, Mcl-1, XIAP, cyclin A, cyclin B, CDK1, and CDK2 and upregulation of p27, Bax, and Bad. These findings suggest that FNQ-mediated cytotoxicity of Ca9-22 cells is related with the G2/M cell cycle arrest and apoptosis via inactivation of Src and PI3K/Akt-mediated signaling pathways.
authors.affiliation: Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kuei-Li
authors.initials: KL
authors.lastname: Lin
authors.affiliation: Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Ming
authors.initials: CM
authors.lastname: Chien
authors.affiliation: Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.affiliation: National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.affiliation: Kaohsiung Medical University, Kaohsiung, Taiwan shreli@kmu.edu.tw.
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D032407:Avicennia / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005663:Furans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009285:Naphthoquinones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C412373:AG 1879; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D009285:Naphthoquinones; D011743:Pyrimidines; C556022:furano-1,2-naphthoquinone; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9