Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells.
Lung cancer is one of the most common causes of cancer death due to its high metastasis potential. The process of cancer migration is an early step that is required for successful metastasis. The discovery and development of natural compounds for cancer therapy have garnered increasing attention in recent years. Gigantol (1) is a bibenzyl compound derived from the Thai orchid, Dendrobium draconis. It exhibits significant cytotoxic activity against several cancer cell lines; however, until recently, the role of 1 on tumor metastasis has not been characterized. This study demonstrates that 1 suppresses the migratory behavior of non-small cell lung cancer H460 cells. Western blot analysis reveals that 1 down-regulates caveolin-1 (Cav-1), activates ATP-dependent tyrosine kinase (phosphorylated Akt at Ser 473), and cell division cycle 42 (Cdc42), thereby suppressing filopodia formation. The inhibitory effect of 1 on cell movement is also exhibited in another lung cancer cell line, H292, but not in normal human keratinocytes (HaCat). The inhibitory activity of 1 on lung cancer migration suggests that this compound may be suitable for further development for the treatment of cancer metastasis.
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University , Bangkok 10330, Thailand.
Sopanya
S
Charoenrungruang
Pithi
P
Chanvorachote
Boonchoo
B
Sritularak
Varisa
V
Pongrakhananon
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D051242:Caveolin 1 / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D031667:Dendrobium / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D001632:Bibenzyls; D051242:Caveolin 1; C478099:gigantol; D006139:Guaiacol; D051057:Proto-Oncogene Proteins c-akt