Abstract:
Resistance to anoikis, enhance cell motility, and growth in anchorage-independent condition are hallmarks of highly metastatic cancer cells. The present study demonstrates anoikis sensitizing and anti-migration activities of Dendrofalconerol A (DF-A), a pure bis(bibenzyls) isolated from stem of Dendrobium falconeri (Orchidaceae), and its underlying mechanisms in human lung cancer H460 cells. DF-A at non-toxic concentrations significantly increased anoikis response of the cancer cells, but caused no toxic effect on normal keratinocytes. In addition, DF-A significantly inhibited the growth of lung cancer cells in anchorage-independent condition. Western blot analysis revealed that anoikis sensitizing effect of such compound involves its ability to suppress survival signals as well as anti-apoptotic proteins, namely, activated protein kinase B (Akt) and Bcl-2. Furthermore, DF-A significantly decreased the level of Caveolin-1 (Cav-1) proteins while has no effect on pro-apoptotic Bax protein and anti-apoptotic Mcl-1 protein. In case of cancer cell motility, we found that DF-A exhibited strong anti-migration activity with the underlying mechanism involves the effect of compound to suppress pFAK and Rho-GTP in lung cancer cells. Finally, we tested the effect of DF-A on chemotherapeutic agent. DF-A exerts no significant effects on susceptibility of cancer cells to cisplatin and etoposide. Taken together, DF-A possesses anoikis sensitizing activity along with anti-migration effect which may be developed as a novel active compounds used for cancer treatment.
