Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand.
J Biomed Sci. 2018 Apr 9;25(1):32. doi: 10.1186/s12929-018-0435-3.
During 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.
Anoikis 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.
Avicequinone 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.
Avicequinone B sensitized anoikis in human lung cancer cells through down-regulation of anti-apoptosis proteins and integrin-mediated survival signaling.
在转移过程中，癌细胞需要抗凋亡抵抗机制才能存活下来，直到到达远处的继发性组织。由于促凋亡敏感可能有益于癌症治疗，本研究表明，一种天然呋喃萘醌，来自红树林（番荔枝科）的 vicenin B，在人类肺癌细胞中具有促凋亡敏感性的潜力。
在超低附着平板中培养人肺癌 H460、H292 和 H23 细胞，用非细胞毒性浓度的 vicenin B 诱导凋亡。用 XTT 测定法在 0-24 h 的孵育时间内评估分离细胞的活力。软琼脂试验用于研究 vicenin B 对锚定非依赖性生长的抑制作用。通过 Western blot 分析阐明了凋亡调节分子（包括存活和凋亡蛋白）的改变。
vicenin B 在 4 μM 时可显著诱导人肺癌细胞在分离条件下的凋亡，并抑制增殖。在 vicenin B 处理的细胞中检测到抗凋亡蛋白的减少，包括抗凋亡蛋白 B 细胞淋巴瘤 2（Bcl-2）和髓样细胞白血病 1（Mcl-1），同时整合素/粘着斑激酶（FAK）/原癌基因酪氨酸蛋白激酶（Src）信号也减弱。
vicenin B 通过下调抗凋亡蛋白和整合素介导的存活信号，使人类肺癌细胞对凋亡敏感。
