A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Abstract

Metastatic cancer cells have been shown to have aggressive behaviors accounting for the high incidence of chemotherapeutic failure and mortality. Because migration and invasion are crucial behaviors for cancer cell dissemination, promising compounds exhibiting potential antimigration effects are of interest for metastasis-based therapeutic approaches. This study aimed to evaluate the activity of a bibenzyl, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), isolated from Dendrobium ellipsophyllum Tang and Wang, in the suppression of migration in human lung cancer cells. TDB at nontoxic concentrations (1 and 5 µM) significantly inhibited the motility of lung cancer cells in scratch-wound assay. Chemotaxis-induced migration and invasion assays also revealed that the cell motility dramatically diminished in the cells treated with 1-5 µM TDB. Western blot analysis provided the underlying molecular mechanism, showing that TDB reduced such cell migration and invasion by decreasing migration-regulating proteins, including integrins αv, α4, β1, β3 and β5, as well as downstream signaling proteins, such as activated focal adhesion kinase (pFAK), activated Ras-related C3 botulinum toxin substrate 1 (Rac1-GTP) and cell division control protein 42 (Cdc42). As the presence of cellular protrusion, called filopodia, has been indicated as a hallmark of migrating cells, we showed that the reduction of the mentioned proteins correlated well with the disappearance of filopodia. In summary, this study demonstrates the promising activity of TDB and its mechanism in the inhibition of lung cancer cell migration, which might be useful for encouraging the development of this compound for antimetastatic approaches.

Effects ofPanax notoginsengon the Metastasis of Human Colorectal Cancer Cells

“…Our results demonstrate that the PNEE increases E-cadherin expression to maintain the integrity of cell-cell stroma. Previous studies have also shown that ethanol-soluble extracts of Cochinchina momordica seeds, an anticancer ingredient in China, and bibenzyl, an active component of Dendrobium ellipsophyllum, can inhibit the epithelial-to-mesenchymal transition (EMT) by increasing the level of E-cadherin in human lung cancer A549 and H292 cells, respectively, resulting in the inhibition of human lung cancer cell migration and invasion (Chaotham et al, 2014;Shen et al, 2015). The suppressive effect of the PNEE on migration and invasion may be an important factor that contributes to the observed antimigration effect.…”

Recent Progress on the Molecular Mechanisms of Anti-invasive and Metastatic Chinese Medicines for Cancer Therapy

“…Geraniin has been shown to inhibit TGF-β1-induced EMT of lung cancer A549 cells in vitro by inducing the epithelial marker E-cadherin and suppressing Snail and mesenchymal marker N-cadherin and vimentin [26]. A compound derived from Dendrobium ellipsophyllum, bibenzyl 4,5,4′ -trihydroxy-3,3′-dimethoxybibenzyl was shown to inhibit EMT of lung cancer cells via downregulating EMT markers (vimentin and Snail) and upregulating E-cadherin [27]. Such EMT suppression was also observed in lung cancer cells treated with other single compounds obtained from Chinese medicine, such as moscatilin [28], gigantol [29], and epicatechin-3-gallate [30].…”

Potential Anti-metastasis Natural Compounds for Lung Cancer

“…Several natural products have been shown to have abilities to suppress EMT in lung cancer cells. A bibenzyl 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl [TDB,7], isolated from Dendrobium ellipsophyllum, has been demonstrated to inhibit EMT and sensitize lung cancer cells to anoikis (57). Treatment of lung cancer cells with non-toxic concentrations of TDB significantly suppressed EMT markers, namely vimentin and Snail, while increased the level of E-cadherin.…”

“…Treatment of lung cancer cells with non-toxic concentrations of TDB significantly suppressed EMT markers, namely vimentin and Snail, while increased the level of E-cadherin. Also, such a decrease in EMT phenotypes was shown to induce anoikis and decrease cell growth in detached conditions by reduction of activated protein kinase B (p-AKT) and activated extracellular signalregulated kinase (p-ERK) (57). Gigantol [8], extracted from Dendrobium draconis, and known bibenzyl compounds, including moscatilin [9], chrysotobibenzyl [10], chrysotoxine [11] and crepidatin [12], isolated from Dendrobium pulchellum, have been demonstrated to suppress EMT in a lung cancer cell model and such suppression resulted in the induction of anoikis and decreased growth in an anchorage-independent manner (58,59).…”