Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells.

Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT). Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT), thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis.

The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells.

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.

Molecular signalings in keloid disease and current therapeutic approaches from natural based compounds.

CONTEXT: Keloid is an excessive dermal scar occurring in response to skin injuries. Several therapeutic strategies have been proposed to ease the aggressiveness of keloid scarring. Even though the principle mechanism underlying the disease propagation still remains unidentified, several signaling pathways were highly focused as plausible pathways involving keloid formation, including transforming growth factor-beta 1 (TGF-ß1), mitogen-activated protein kinase (MAPK), insulin-like growth factor-I (IGF-I), and integrin pathways. Natural compounds containing multiple bioeffective properties such as quercetin, asiaticoside, Astragalus membranaceus Bunge. (Leguminosae), and Salvia miltiorrhiza Bunge. (Lamiaceae) extracts, curcuminoids, oxymatrine, madecassoside, and Aneilema keisak Hassk. (Commelinaceae) are claimed as candidates for therapeutic treatment against keloid disorder. OBJECTIVE: This review investigates current mechanisms regarding keloid formation and provides scientific evidence supporting the therapeutic potential of natural compounds. METHODS: This review obtained and analyzed a number of literature data items from various databases including Pubmed, ScienceDirect, and Elton B. Stephens Company (EBSCO). RESULT: Several phytochemical compounds are able to suppress keloid scar development through manipulating various components in the complex signaling cascades. CONCLUSION: The present review may be helpful to future studies that further examine the molecular mechanism of keloid etiology as well as investigate the anti-keloid property in natural compounds.