Biological and Environmental Sciences Department, Home Economic Faculty, Al Azhar University, Tanta 31732, Egypt.
Biochemistry Department, Faculty of Science, University of Tabuk, Tabuk 47512, Saudi Arabia.
Molecules. 2021 May 31;26(11):3303. doi: 10.3390/molecules26113303.
The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (, caspase3, and ) and decreased expression of the anti-apoptotic gene ; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator and its downstream target ; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene and upregulation of the anti-migratory gene ; and (5) downregulation of inflammation-related genes ( and ). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.
昆虫作为一种可行且有用的天然产物资源,在替代医学中是一种新颖且有前途的选择。已经发现昆虫及其幼虫的几种成分能够抑制癌症不同阶段的分子途径。本研究旨在分析幼虫的水提物和醇提物对乳腺癌 MCF7 细胞的影响,并探讨其潜在机制。我们的结果表明,单独使用 5%水提或醇提幼虫提取物可抑制 MCF7 增殖,但对正常 Vero 细胞无细胞毒性作用。抗癌作用是通过(1)诱导细胞凋亡来介导的,表现为凋亡基因(、caspase3 和)表达增加,抗凋亡基因表达减少;(2)抑制细胞内活性氧;(3)抗氧化酶(CAT、SOD 和 GPx)升高和抗氧化调节剂及其下游靶基因上调;(4)体外划痕愈合试验显示的迁移抑制和迁移相关基因下调和抗迁移基因上调;以及(5)炎症相关基因(和)下调。水提物表现出最佳的抗癌效果,具有较高的抗氧化活性,但抗炎特性低于醇提物。HPLC 分析表明,水提物中含有几种黄酮类和酚类化合物,其中白藜芦醇和柚皮素的浓度最高,而醇提物中迷迭香酸的浓度最高。这是第一个解释幼虫黄酮类和酚类化合物丰富提取物通过启动细胞凋亡、激活抗氧化剂以及抑制迁移和炎症来诱导 MCF7 细胞活力丧失的细胞内途径的报告。因此,这些提取物可作为抗癌药物的佐剂以及抗氧化剂和抗炎剂使用。