Abstract
BackgroundDuring metastasis, cancer cells require anokis resistant mechanism to survive until reach the distant secondary tissues. As anoikis sensitization may benefit for cancer therapy, this study demonstrated the potential of avicequinone B, a natural furanonaphthoquinone found in mangrove tree (Avicenniaceae) to sensitize anoikis in human lung cancer cells.MethodsAnoikis inducing effect was investigated in human lung cancer H460, H292 and H23 cells that were cultured in ultra-low attachment plate with non-cytotoxic concentrations of avicequinone B. Viability of detached cells was evaluated by XTT assay at 0–24 h of incubation time. Soft agar assay was performed to investigate the inhibitory effect of avicequinone B on anchorage-independent growth. The alteration of anoikis regulating molecules including survival and apoptosis proteins were elucidated by western blot analysis.ResultsAvicequinone B at 4 μM significantly induced anoikis and inhibited proliferation under detachment condition in various human lung cancer cells. The reduction of anti-apoptotic proteins including anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1) associating with the diminution of integrin/focal adhesion kinase (FAK)/Proto-oncogene tyrosine-protein kinase (Src) signals were detected in avicequinone B-treated cells.ConclusionsAvicequinone B sensitized anoikis in human lung cancer cells through down-regulation of anti-apoptosis proteins and integrin-mediated survival signaling.
Highlights
During metastasis, cancer cells require anokis resistant mechanism to survive until reach the distant secondary tissues
Anoikis is inhibited by the increase of survival signals through the modulation of integrins expression contributing activation of Focal adhesion kinase (FAK)/Proto-oncogene tyrosine-protein kinase (Src) and PI3K/Phospho kinase B (AKT) pathway [10,11,12,13,14]
Cytotoxicity of avicequinone B in human lung cancer cells To investigate the effect of avicequinone B on anoikis, the cytotoxicity of the compound in lung cancer H460 cells was firstly elucidated
Summary
Cancer cells require anokis resistant mechanism to survive until reach the distant secondary tissues. Metastasis or the spreading of cancer cells from primary site to secondary vital organs is a major cause of mortality in the lung cancer [2, 3]. According to highly metastatic features, most of lung cancer patients are frequently diagnosed at advanced stage presenting dissemination of tumor pathology [4, 5]. Such concepts lead to the urgent need for anti-metastasis therapy for lung cancer. In order to survive in blood or lymphatic circulation, certain cancer cells acquire anoikis resistance mechanisms. Anoikis is inhibited by the increase of survival signals through the modulation of integrins expression contributing activation of FAK (focal adhesion kinase)/Src (proto-oncogene tyrosineprotein kinase) and PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase)/AKT (phospho kinase B) pathway [10,11,12,13,14]
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