Von Fournier Armin, Kasemo Totta Ehret, Hackenberg Stephan, Wilhelm Christian, Meyer Till, Gehrke Thomas, Hagen Rudolf, Scherzad Agmal
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Wuerzburg, D-97080 Wuerzburg, Germany.
Oncol Lett. 2024 Jun 26;28(2):400. doi: 10.3892/ol.2024.14533. eCollection 2024 Aug.
α-solanine is a glycoalkaloid that is commonly found in nightshades () and has a toxic effect on the human organism. Among other things, it is already known to inhibit tumor cell proliferation and induce apoptosis in tumor cell lines. Due to its potential as a tumor therapeutic, the current study investigated the effect of α-solanine on head and neck squamous cell carcinoma (HNSCC). In addition, genotoxic and antiangiogenic effects on human umbilical vein endothelial cells (HUVECs) were evaluated at subtoxic α-solanine concentrations. Cytotoxicity and apoptosis rates were measured in two human HNSCC cell lines (FaDu pharynx carcinoma cells and CAL-33 tongue carcinoma cells), as well as in HUVECs. MTT and Annexin V analyses were performed 24 h after α-solanine treatment at increasing doses up to 30 µM to determine cytotoxic concentrations. Furthermore, genotoxicity at subtoxic concentrations of 1, 2, 4 and 6 µM in HUVECs was analyzed using single-cell gel electrophoresis (comet assay). The antiangiogenic effect on HUVECs was evaluated in the capillary tube formation assay. The MTT assay indicated an induction of concentration-dependent viability loss in FaDu and CAL-33 cancer cell lines, whereas the Annexin V test revealed α-solanine-induced cell death predominantly independent from apoptosis. In HUVECs, the cytotoxic effect occurred at lower concentrations. No genotoxicity or inhibition of angiogenesis were detected at subtoxic doses in HUVECs. In summary, α-solanine had a cytotoxic effect on both malignant and non-malignant cells, but this was only observed at higher concentrations in malignant cells. In contrast to existing data in the literature, tumor cell apoptosis was less evident than necrosis. The lack of genotoxicity and antiangiogenic effects in the subtoxic range in benign cells are promising, as this is favorable for potential therapeutic applications. In conclusion, however, the cytotoxicity in non-malignant cells remains a severe hindrance for the application of α-solanine as a therapeutic tumor agent in humans.
α-茄碱是一种常见于茄科植物中的糖苷生物碱，对人体有机体具有毒性作用。除此之外，已知它能抑制肿瘤细胞增殖并诱导肿瘤细胞系凋亡。鉴于其作为肿瘤治疗剂的潜力，当前研究调查了α-茄碱对头颈部鳞状细胞癌（HNSCC）的影响。此外，还在亚毒性α-茄碱浓度下评估了其对人脐静脉内皮细胞（HUVECs）的遗传毒性和抗血管生成作用。在两个人类HNSCC细胞系（FaDu咽癌细胞和CAL-33舌癌细胞）以及HUVECs中测量了细胞毒性和凋亡率。在α-茄碱以高达30 μM的递增剂量处理24小时后，进行MTT和膜联蛋白V分析以确定细胞毒性浓度。此外，使用单细胞凝胶电泳（彗星试验）分析了HUVECs中1、2、4和6 μM亚毒性浓度下的遗传毒性。在毛细管形成试验中评估了对HUVECs的抗血管生成作用。MTT试验表明FaDu和CAL-33癌细胞系中存在浓度依赖性活力丧失诱导现象，而膜联蛋白V试验显示α-茄碱诱导的细胞死亡主要独立于凋亡。在HUVECs中，细胞毒性作用在较低浓度下发生。在HUVECs的亚毒性剂量下未检测到遗传毒性或血管生成抑制。总之，α-茄碱对恶性和非恶性细胞均具有细胞毒性作用，但仅在恶性细胞的较高浓度下观察到。与文献中的现有数据相反，肿瘤细胞凋亡不如坏死明显。良性细胞在亚毒性范围内缺乏遗传毒性和抗血管生成作用是有前景的，因为这有利于潜在的治疗应用。然而，总的来说，非恶性细胞中的细胞毒性仍然是α-茄碱作为人类治疗肿瘤药物应用的严重障碍。
