gigantol and Lung-Neoplasms

Lung cancer has been the major cause of death within patients due to the high metastatic rate. One of the most essential processes of metastasis is the ability of cancer cells to resist the programmed cell death in a detached condition called anoikis. The discoveries of new natural compound that is able to sensitize anoikis in cancer cells have garnered the most interest in cancer pharmaceutical science. Gigantol, a bibenzyl compound extracted from Dendrobium draconis, has been a promising natural derived compound for cancer therapy due to several cytotoxic effects in cancer cells. This study has demonstrated for the first time that gigantol significantly decreases lung cancer cells' viability in a detached condition through anoikis and anchorage-independent assays. Western blotting analysis reveals that gigantol greatly decreases epithelial to mesenchymal transition (EMT) markers including N-cadherin, vimentin, and Slug leading to a significant suppression of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and caveolin-1 (cav-1) survival pathways during the detached condition. Therefore, gigantol could be a potential cancer therapeutic compound suggesting for further development for cancer therapy.

Topics: Anoikis; Apoptosis; Bibenzyls; Blotting, Western; Cadherins; Carcinoma, Non-Small-Cell Lung; Caveolin 1; Cell Proliferation; Epithelial-Mesenchymal Transition; Extracellular Signal-Regulated MAP Kinases; Guaiacol; Humans; Lung Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction; Tumor Cells, Cultured; Vimentin

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.

Topics: Antineoplastic Agents; Bibenzyls; Carcinoma, Non-Small-Cell Lung; Caveolin 1; Cell Movement; Cell Proliferation; Cell Survival; Dendrobium; Drug Screening Assays, Antitumor; Guaiacol; Humans; Keratinocytes; Lung Neoplasms; Molecular Structure; Proto-Oncogene Proteins c-akt; Signal Transduction