Mahmud Md Ashiq, Siddique Abu Bakar, Tajmim Afsana, King Judy Ann, El Sayed Khalid A
Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Foundational and Clinical Sciences Department, Thomas F. Frist, Jr. College of Medicine, Belmont University, 1900 Belmont Boulevard, Nashville, TN 37212, USA.
Molecules. 2025 Jan 1;30(1):139. doi: 10.3390/molecules30010139.
Melanoma is among the most abundant malignancies in the US and worldwide. Ligstroside aglycone (LA) is a rare extra-virgin olive oil-derived monophenolic secoiridoid with diverse bioactivities. LA dose-response screening at the NCI 60 cancer cells panel identified the high sensitivity of the Malme-3M cell line, which harbors a mutation. Daily oral 10 mg/kg LA exhibited potent in vivo antitumor effects against Malme-3M cells xenograft in a nude mouse model by targeting the BRAF signaling pathway. A human Clariom S microarray analysis of the collected Malme- 3M tumors identified 571 dysregulated genes, with the downregulation of pathways critical for melanoma cells growth and survival. A Western blot analysis of the collected animal tumors further validated the downregulation of the mutated BRAF-MAPK axis, as well as the GPD1 and ELOVL6 expression levels. A histopathological analysis of Malme-3M tumor sections showed extensive focal tumor necrosis in treated mice. An immunofluorescence study of tumor sections showed notable reductions in proliferation marker ki67 and the vasculogenesis marker CD31 in treated tumors. These findings promote LA as a potential nutraceutical lead for the control of the mutant melanoma.
黑色素瘤是美国和全球范围内最常见的恶性肿瘤之一。裂环烯醚萜苷元（LA）是一种罕见的特级初榨橄榄油衍生的单酚类裂环烯醚萜，具有多种生物活性。在NCI 60癌细胞面板上进行的LA剂量反应筛选确定了携带一种突变的Malme-3M细胞系具有高敏感性。每日口服10 mg/kg的LA通过靶向BRAF信号通路，对裸鼠模型中Malme-3M细胞异种移植瘤表现出强大的体内抗肿瘤作用。对收集的Malme-3M肿瘤进行的人类Clariom S微阵列分析确定了571个失调基因，其中对黑色素瘤细胞生长和存活至关重要的通路被下调。对收集的动物肿瘤进行的蛋白质免疫印迹分析进一步证实了突变的BRAF-MAPK轴以及GPD1和ELOVL6表达水平的下调。对Malme-3M肿瘤切片的组织病理学分析显示，治疗小鼠中出现广泛的局灶性肿瘤坏死。对肿瘤切片的免疫荧光研究显示，治疗后的肿瘤中增殖标志物ki67和血管生成标志物CD31显著减少。这些发现促使LA成为控制突变型黑色素瘤的潜在营养保健品先导物。
