Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Institut Bonanova, Circumval·lació 8, 08003 Barcelona, Spain.
Biomed Pharmacother. 2022 Oct;154:113584. doi: 10.1016/j.biopha.2022.113584. Epub 2022 Aug 24.
Neuroblastoma (NB) is one of the most common solid pediatric tumors and especially high-risk NBs still account for about 12-15% of cancer related deaths in children. Kigelia africana (KA) is a plant used in traditional African medicine which has already shown its anti-cancer potential in several in vitro and in vivo studies. The aim of this study is to evaluate the effect of KA fruit extract on stage 4 high-risk NB cells. Therefore, NB cell lines with and without MYCN amplification and non-neoplastic cells were treated with KA fruit extract at different concentrations. The effect of KA on cell viability and apoptosis rate were assessed by bioluminescence-/fluorescence-based assays. Several proteins involved in survival, tumor growth, inflammation and metastasis were detected via western blot and immunofluorescence. Secreted cytokines were detected via ELISA. Phytochemical composition of the extract was analyzed by liquid chromatography with tandem mass spectrometry (LC/MS/MS). Our group demonstrates a dose- and time-dependent selective cytotoxic effect of KA fruit extract on NB, especially in MYCN non-amplified tumor cells, by inhibiting cell proliferation and inducing cell death. Western blot and immunofluorescence results demonstrate a regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), disialoganglioside GD2 and epidermal growth factor receptor (EGFR) in KA-treated tumor cells. Our results evidence striking anti-cancer properties of KA fruit and pave the way for further surveys on the therapeutic properties and mechanisms of action in NB.
神经母细胞瘤(NB)是最常见的儿童实体肿瘤之一,特别是高危 NB 仍然约占儿童癌症相关死亡的 12-15%。Kigelia africana(KA)是一种用于传统非洲医学的植物,已经在几项体外和体内研究中显示出其抗癌潜力。本研究旨在评估 KA 果实提取物对 4 期高危 NB 细胞的影响。因此,用不同浓度的 KA 果实提取物处理有和无 MYCN 扩增的 NB 细胞系和非肿瘤细胞。通过生物发光/荧光测定法评估 KA 对细胞活力和凋亡率的影响。通过 Western blot 和免疫荧光检测参与存活、肿瘤生长、炎症和转移的几种蛋白质。通过 ELISA 检测分泌的细胞因子。通过液相色谱-串联质谱(LC/MS/MS)分析提取物的植物化学成分。我们的研究小组证明了 KA 果实提取物对 NB 的剂量和时间依赖性选择性细胞毒性作用,特别是在 MYCN 非扩增肿瘤细胞中,通过抑制细胞增殖和诱导细胞死亡。Western blot 和免疫荧光结果表明,KA 处理的肿瘤细胞中核因子 kappa-轻链增强子的 B 细胞(NF-κB)、二唾液酸神经节苷脂 GD2 和表皮生长因子受体(EGFR)受到调节。我们的结果证明了 KA 果实的显著抗癌特性,并为进一步研究 NB 中的治疗特性和作用机制铺平了道路。