Ausawasamrit Apisara, Itthiwarapornkul Nattawut, Chaotham Chatchai, Sukrong Suchada, Chanvorachote Pithi
Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Anticancer Res. 2015 May;35(5):2827-34.
BACKGROUND/AIM: The ability of cancer cells to resist to anoikis has been shown to augment cancer cell metastasis in many cancers. In search for potential substances for anti-metastatic approaches, this study aimed to investigate anoikis-sensitizing activity of lupalbigenin, extracted from Derris scandens.
Human lung cancer cells were treated with non-cytotoxic concentrations of lupalbigenin in a detachment condition. Anoikis was evaluated at various time points using MTT viability assays. The effect of lupalbigenin on anchorage-independent growth was performed by soft-agar assay. The survival signaling proteins, as well as regulatory proteins of apoptosis and metastasis, were examined by western blot analysis.
Lupalbigenin treatment significantly down-regulated survival proteins, including protein kinase B (pAKT/AKT) and extracellular signal-regulated kinase (pERK/ERK), as well as anti-apoptotic protein B-cell lymphoma 2 (BCL-2), resulting in the enhancement of the cellular response to anoikis and the decrease of growth and survival in an anchorage-independent condition.
Lupalbigenin sensitizes detachment-induced cell death in human lung cancer cell through down-regulation of pro-survival proteins.
背景/目的:癌细胞抵抗失巢凋亡的能力已被证明在许多癌症中会增强癌细胞转移。为了寻找抗转移方法的潜在物质,本研究旨在研究从鱼藤中提取的刺桐吉宁的失巢凋亡敏化活性。
在脱离条件下,用人肺癌细胞用非细胞毒性浓度的刺桐吉宁处理。使用MTT活力测定法在不同时间点评估失巢凋亡。通过软琼脂测定法检测刺桐吉宁对非锚定依赖性生长的影响。通过蛋白质印迹分析检查存活信号蛋白以及凋亡和转移的调节蛋白。
刺桐吉宁处理显著下调存活蛋白,包括蛋白激酶B(pAKT/AKT)和细胞外信号调节激酶(pERK/ERK),以及抗凋亡蛋白B细胞淋巴瘤2(BCL-2),导致细胞对失巢凋亡的反应增强,以及在非锚定依赖性条件下生长和存活的减少。
刺桐吉宁通过下调促存活蛋白使人类肺癌细胞中脱离诱导的细胞死亡敏感化。