Regulatory effects of Siegesbeckia glabrescens on non-small cell lung cancer cell proliferation and invasion.
Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70(S6K) as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70(S6K). In contrast, in H1299 cells the inactivation of p38(MAPK) appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.
College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
Ha Neul
HN
Lee
Ji-Hye
JH
Joo
Joa Sub
JS
Oh
Shin Wook
SW
Choi
Dong-Wan
DW
Seo
D000972:Antineoplastic Agents, Phytogenic; D019659:Asteraceae / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D000431:Ethanol; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D000431:Ethanol; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048051:p38 Mitogen-Activated Protein Kinases