Avicequinone B sensitizes anoikis in human lung cancer cells

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.

Transcriptome Changes in Colorectal Cancer Cells upon Treatment with Avicequinone B

“…As can be seen in Figure 2A green fluorescence). This result differs from that obtained by Prateep et al 8 who reported the induction of apoptosis, but not necrosis, in H460 cells treated with avicequinone B. This discrepancy might be explained by the differences in the experimental setting, since they used a mild test concentration (lower than the IC 50 ).…”

“…Notably, ERK activation/expression is involved in the cellular response to environment regulating cell cycle and cellular differentiation and senescence, which is critical for cancer initiation and progression ( Figure S4). In agreement, Patreep et al 8 demonstrated that the inhibition of ERK phosphorylation by avicequinone B is an important mechanism involved in the induction of detachment-induced cell death, also known as anoikis, in resistant lung cancer cells. Taken together, this experimental evidence demonstrates that ERK-related signaling pathways play an important role in the cytotoxic effect of the test compound against cancer cells.…”

“…As we recently reported, 15 , and NCI-H460) adenocarcinoma [8][9][10][11] ; we continued the pharmacological study of the test compound using CRC cells.…”

“…[4][5][6][7] Among them, naphtho [2,3-b]furan-4,9-dione (avicequinone B) and other structurally-related annulated furan derivatives such as naphtho [1,2-b]furan-4,5-dione, have demonstrated outstanding cytotoxicity against cancer cells. [8][9][10][11] Avicequinone B was first isolated by Ito et al 6 in 2000 from the stem bark of A. alba, and later described by Jia et al 12 in the leaves of A. marina. Interestingly, the bioactivity of avicequinone B was enthusiastically studied since 1994, when Koyanagi et al 13 proposed a reliable method for its chemical synthesis; at a time when it was consider an unnatural analogue or a mere precursor during the biosynthetic process.…”

“… 4 - 7 Among them, naphtho[2,3- b ]furan-4,9-dione (avicequinone B) and other structurally-related annulated furan derivatives such as naphtho[1,2- b ]furan-4,5-dione, have demonstrated outstanding cytotoxicity against cancer cells. 8 - 11 …”