Schultz Chad R, Gruhlke Martin C H, Slusarenko Alan J, Bachmann André S
Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, U.S.A.
Society for Natural Product and Drug Research (GENAWIF), Aachen, Germany.
In Vivo. 2025 May-Jun;39(3):1283-1292. doi: 10.21873/invivo.13932.
BACKGROUND/AIM: Allicin is a small-molecule natural product found in garlic (Allium sativum). We previously showed that allicin inhibits ornithine decarboxylase (ODC) and induces apoptotic cell death in pediatric neuroblastoma (NB) cancer cell cultures. However, its potency as an anticancer agent has not been sufficiently explored.
In this study, we used cell proliferation assays, immunoblotting techniques, and light microscopy to study NB tumor cell cultures and human primary neonatal skin fibroblast control cells as well as a -amplified NB patient-derived xenograft (PDX) mouse tumor model to study the efficacy of allicin .
Allicin strongly inhibits NB tumor cell proliferation in a dose-dependent manner while non-cancerous human primary neonatal skin fibroblast control cells were largely unaffected. Importantly, two intra-tumoral injections of allicin over a two-week trial period significantly reduced the NB tumor burden in mice compared to controls (N=4-9 mice/group). Excised tumor tissues revealed that allicin treatment increased the cyclin-dependent kinase inhibitor p27 protein levels, suggesting that , allicin increases p27-mediated G/S cell cycle arrest.
Our findings warrant further preclinical development of allicin as a potential anticancer agent, especially for those types of cancers that are treatable by intra-tumoral injections, including neuroblastoma, glioblastoma, and medulloblastoma.
背景/目的：大蒜素是一种存在于大蒜（葱属植物）中的小分子天然产物。我们之前表明大蒜素在小儿神经母细胞瘤（NB）癌细胞培养物中可抑制鸟氨酸脱羧酶（ODC）并诱导凋亡性细胞死亡。然而，其作为抗癌剂的效力尚未得到充分研究。
在本研究中，我们使用细胞增殖测定、免疫印迹技术和光学显微镜来研究NB肿瘤细胞培养物和人原代新生儿皮肤成纤维细胞对照细胞，以及一个α扩增的NB患者来源的异种移植（PDX）小鼠肿瘤模型来研究大蒜素的疗效。
大蒜素以剂量依赖性方式强烈抑制NB肿瘤细胞增殖，而非癌性人原代新生儿皮肤成纤维细胞对照细胞基本未受影响。重要的是，在为期两周的试验期内，与对照组相比，两次瘤内注射大蒜素显著降低了小鼠的NB肿瘤负荷（每组4 - 9只小鼠）。切除的肿瘤组织显示，大蒜素处理增加了细胞周期蛋白依赖性激酶抑制剂p27的蛋白水平，这表明大蒜素增加了p27介导的G/S期细胞周期阻滞。
我们的研究结果为大蒜素作为一种潜在抗癌剂的进一步临床前开发提供了依据，特别是对于那些可通过瘤内注射治疗的癌症类型，包括神经母细胞瘤、胶质母细胞瘤和髓母细胞瘤。
