Abstract：
BACKGROUND: Euphorbia helioscopia L (EHL), a widely used medicinal plant in traditional Chinese medicine, has shown promising effects on certain cancers. However, previous studies on EHL did not elucidate the underlying molecular mechanisms. Herein, for the first time, we present the strong therapeutic potential of EHL extracts on malignant hemangioendothelioma, a rare type of vascular tumor.
OBJECTIVE: To investigate the potential anti-tumor mechanism of extracts of EHL on hemangioendothelioma and melanoma.
METHODS: The dried stems and leaves of EHL were extracted with Ethyl Acetate and n-Butyl alcohol, yielding two crude extracts Ethyl Acetate fraction (EA) and n-Butyl alcohol fraction (Bu). EA and Bu were prepared to assess the potential mechanism by assays for cell proliferation, cell cycle, apoptosis, colony formation, tube formation, cellular metabolic activity, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, RNA expression and western blot. To further confirm the anti-tumor effect of EHL in vivo, we established hemangioendothelioma and melanoma tumor-bearing mouse model using node mice and administered with EA and Bu, tracked alterations in tumor volume and survival rate. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations.
RESULTS: We demonstrate that the injection of EA and Bu, significantly inhibits tumor growth and prolongs the lifespan of tumor-bearing mice. Bu treatment exhibited a remarkable 33 % healing effect on the primary hemangioendothelioma tumor, bringing the survival rate to a level comparable to that of healthy mice. Mechanically, both EA and Bu impair respiratory chain complexes, leading to mitochondrial dysfunction and accumulation of reactive oxygen species (ROS), resulting in DNA damage, cell apoptosis, and finally blocked angiogenesis. While EA demonstrates robust inhibitory effects on cancer cell growth and a broader impact on metabolism in vitro, the in vivo effect of Bu surpasses that of EA in terms of strength. EA and Bu also exhibit potent anti-tumor effects on a primary melanoma model by inhibiting angiogenesis. Importantly, when compared to other compounds used in the treatment of hemangioendothelioma, EA and Bu demonstrate more profound anti-tumor effects.
CONCLUSIONS: For the first time, our findings reveal that EHL extracts, especially the high polarity compounds, exhibit potent anti-tumor effects by targeting cellular metabolism, specifically through the inhibition of mitochondria-related metabolic activities. This leads to the accumulation of ROS and effectively suppresses abnormal angiogenesis.
OBJECTIVE: To investigate the potential anti-tumor mechanism of extracts of EHL on hemangioendothelioma and melanoma.
METHODS: The dried stems and leaves of EHL were extracted with Ethyl Acetate and n-Butyl alcohol, yielding two crude extracts Ethyl Acetate fraction (EA) and n-Butyl alcohol fraction (Bu). EA and Bu were prepared to assess the potential mechanism by assays for cell proliferation, cell cycle, apoptosis, colony formation, tube formation, cellular metabolic activity, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, RNA expression and western blot. To further confirm the anti-tumor effect of EHL in vivo, we established hemangioendothelioma and melanoma tumor-bearing mouse model using node mice and administered with EA and Bu, tracked alterations in tumor volume and survival rate. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations.
RESULTS: We demonstrate that the injection of EA and Bu, significantly inhibits tumor growth and prolongs the lifespan of tumor-bearing mice. Bu treatment exhibited a remarkable 33 % healing effect on the primary hemangioendothelioma tumor, bringing the survival rate to a level comparable to that of healthy mice. Mechanically, both EA and Bu impair respiratory chain complexes, leading to mitochondrial dysfunction and accumulation of reactive oxygen species (ROS), resulting in DNA damage, cell apoptosis, and finally blocked angiogenesis. While EA demonstrates robust inhibitory effects on cancer cell growth and a broader impact on metabolism in vitro, the in vivo effect of Bu surpasses that of EA in terms of strength. EA and Bu also exhibit potent anti-tumor effects on a primary melanoma model by inhibiting angiogenesis. Importantly, when compared to other compounds used in the treatment of hemangioendothelioma, EA and Bu demonstrate more profound anti-tumor effects.
CONCLUSIONS: For the first time, our findings reveal that EHL extracts, especially the high polarity compounds, exhibit potent anti-tumor effects by targeting cellular metabolism, specifically through the inhibition of mitochondria-related metabolic activities. This leads to the accumulation of ROS and effectively suppresses abnormal angiogenesis.
摘要：
背景：一品红（EHL），一种在中药中广泛使用的药用植物，对某些癌症显示出有希望的效果。然而,先前对EHL的研究未阐明潜在的分子机制.在这里，第一次,我们提出了EHL提取物对恶性血管内皮瘤的强大治疗潜力，一种罕见的血管肿瘤.
目的：探讨EHL提取物对血管内皮瘤和黑色素瘤的潜在抗肿瘤机制。
方法：用乙酸乙酯和正丁醇提取EHL的干茎和叶，得到两个粗提取物乙酸乙酯级分(EA)和正丁醇级分(Bu)。准备EA和Bu通过细胞增殖试验评估潜在的机制，细胞周期,凋亡，菌落形成,管形成,细胞代谢活动，活性氧（ROS），N-乙酰半胱氨酸(NAC)拮抗作用,RNA表达和westernblot。为了进一步证实EHL在体内的抗肿瘤作用,我们使用结瘤小鼠建立了血管内皮瘤和黑色素瘤荷瘤小鼠模型，并给予EA和Bu，跟踪肿瘤体积和生存率的变化。此外，组织样本用于组织学，蛋白质，和基因调查。
结果：我们证明了EA和Bu的注入，显著抑制肿瘤生长，延长荷瘤小鼠的寿命。Bu治疗对原发性血管内皮瘤肿瘤有显著的33%愈合效果，使存活率达到与健康小鼠相当的水平。机械上,EA和Bu都损害呼吸链复合物，导致线粒体功能障碍和活性氧（ROS）的积累，导致DNA损伤,细胞凋亡，最终阻断了血管生成。虽然EA显示出对癌细胞生长的强大抑制作用和对体外代谢的更广泛影响，Bu的体内效果在强度方面超过EA。EA和Bu还通过抑制血管生成对原发性黑素瘤模型表现出有效的抗肿瘤作用。重要的是,与用于治疗血管内皮瘤的其他化合物相比，EA和Bu表现出更深刻的抗肿瘤作用。
结论：第一次，我们的研究结果表明，EHL提取物，尤其是高极性化合物，通过靶向细胞代谢表现出有效的抗肿瘤作用，特别是通过抑制线粒体相关的代谢活动。这导致ROS的积累并有效地抑制异常血管生成。
目的：探讨EHL提取物对血管内皮瘤和黑色素瘤的潜在抗肿瘤机制。
方法：用乙酸乙酯和正丁醇提取EHL的干茎和叶，得到两个粗提取物乙酸乙酯级分(EA)和正丁醇级分(Bu)。准备EA和Bu通过细胞增殖试验评估潜在的机制，细胞周期,凋亡，菌落形成,管形成,细胞代谢活动，活性氧（ROS），N-乙酰半胱氨酸(NAC)拮抗作用,RNA表达和westernblot。为了进一步证实EHL在体内的抗肿瘤作用,我们使用结瘤小鼠建立了血管内皮瘤和黑色素瘤荷瘤小鼠模型，并给予EA和Bu，跟踪肿瘤体积和生存率的变化。此外，组织样本用于组织学，蛋白质，和基因调查。
结果：我们证明了EA和Bu的注入，显著抑制肿瘤生长，延长荷瘤小鼠的寿命。Bu治疗对原发性血管内皮瘤肿瘤有显著的33%愈合效果，使存活率达到与健康小鼠相当的水平。机械上,EA和Bu都损害呼吸链复合物，导致线粒体功能障碍和活性氧（ROS）的积累，导致DNA损伤,细胞凋亡，最终阻断了血管生成。虽然EA显示出对癌细胞生长的强大抑制作用和对体外代谢的更广泛影响，Bu的体内效果在强度方面超过EA。EA和Bu还通过抑制血管生成对原发性黑素瘤模型表现出有效的抗肿瘤作用。重要的是,与用于治疗血管内皮瘤的其他化合物相比，EA和Bu表现出更深刻的抗肿瘤作用。
结论：第一次，我们的研究结果表明，EHL提取物，尤其是高极性化合物，通过靶向细胞代谢表现出有效的抗肿瘤作用，特别是通过抑制线粒体相关的代谢活动。这导致ROS的积累并有效地抑制异常血管生成。
