Dendrofalconerol A sensitizes anoikis and inhibits migration in lung cancer cells.
Resistance to anoikis, enhanced cell motility, and growth in anchorage-independent conditions are hallmarks of highly metastatic cancer cells. The present study demonstrates the anoikis-sensitizing and anti-migration activities of dendrofalconerol A (DF-A), a pure bis(bibenzyl) isolated from the stem of Dendrobium falconeri (Orchidaceae), and its underlying mechanisms in human lung cancer H460 cells. DF-A at non-toxic concentrations significantly increased the anoikis response of the cancer cells, but caused no toxic effect on normal keratinocytes. In addition, DF-A significantly inhibited the growth of lung cancer cells in anchorage-independent conditions. Western blot analysis revealed that the anoikis-sensitizing effect of such a compound involves its ability to suppress survival signals as well as anti-apoptotic proteins, namely, activated protein kinase B (Akt) and Bcl-2. Furthermore, DF-A decreased caveolin-1 (Cav-1), a protein responsible for aggressiveness, while having no effect on Bax, Mcl-1, and activated Erk (p42/44) proteins. In the case of cell motility, DF-A exhibited strong anti-migration activity with the mechanism involving suppression of pFAK and Rho-GTP, but had no effect on Rac-GTP in lung cancer cells. Taken together, DF-A possesses anoikis-sensitizing activity along with anti-migration effects, and may be developed as a novel active compound for cancer treatment.
Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, 10330, Thailand.
Premkamol
P
Pengpaeng
Boonchoo
B
Sritularak
Pithi
P
Chanvorachote
D023102:Anoikis / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001632:Bibenzyls / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D031667:Dendrobium / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014966:Xanthenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
C000595880:4,6-dimethoxy-9-(4-methoxybenzyl)-8-(2-(4-methoxyphenyl)ethyl)-9H-xanthene-2,3,5-triol; D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D014966:Xanthenes