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A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

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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.

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Acknowledgments

This research was supported by the Ratchadapisek Sompoch Endowment Fund (2014) of Chulalongkorn University (CU-57-003-HR). The authors would like to thank the Rachadapisek Somphot Post-Doctoral Fund, Chulalongkorn University, Boonchoo Sritularak and Krich Rajprasit.

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Authors and Affiliations

  1. Cell-Based Drug and Health Product Development Research Unit, Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Chatchai Chaotham

  2. Cell-Based Drug and Health Product Development Research Unit, Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote

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  1. Chatchai Chaotham
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  2. Pithi Chanvorachote
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Correspondence to Pithi Chanvorachote.

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Chaotham, C., Chanvorachote, P. A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells. J Nat Med 69, 565–574 (2015). https://doi.org/10.1007/s11418-015-0925-5

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