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肉豆蔻醚诱导乳腺癌细胞凋亡和调控细胞周期的作用机制研究。

Mechanistic evaluation of myristicin on apoptosis and cell cycle regulation in breast cancer cells.

机构信息

Translational Nanomedicine and Lifestyle Disease Research Laboratory, Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.

Department of Biochemistry, Centre for Advanced Cancer Research, University of Kerala, Thiruvananthapuram, Kerala, India.

出版信息

J Biochem Mol Toxicol. 2024 Jun;38(6):e23740. doi: 10.1002/jbt.23740.

Abstract

The current study was focused on the anticancer activity of myristicin against MCF-7 human breast cancer (BC) cells. BC is the most common and leading malignant disease in women worldwide. Now-a-days, various conventional therapies are used against BC and still represent a chief challenge because those treatments fail to differentiate normal cells from malignant cells, and they have severe side effects also. So, there is a need develop new therapies to decrease BC-related morbidity and mortality. Myristicin, a 1‑allyl‑5‑methoxy‑3, 4‑methylenedioxybenzene, is a main active aromatic compound present in various spices, such as nutmeg, mace, carrot, cinnamon, parsely and some essential oils. Myristicin has a wide range of effects, including antitumor, antioxidative and antimicrobial activity. Nevertheless, the effects of myristicin on human BC cells remain largely unrevealed. The cytotoxicity effect of myristicin on MCF‑7 cells was increased dose dependently detected by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Lactate Dehydrogenase assays. Myristicin was found to be significantly inducing the cell apoptosis, as compared to control, using acridine orange/ethidium bromide, Hoechst stain and annexin V. Moreover, it activates cell antimigration, intracellular reactive oxygen species generation and cell cycle arrest in the G/S phase. In addition, myristicin induces the expression of apoptosis and cell cycle genes (Caspases8, Bax, Bid, Bcl2, PARP, p53, and Cdk1) was demonstrated by quantitative polymerase chain reaction and apoptosis proteins (c-PARP, Caspase 9, Cytochrome C, PDI) expression was also analyzed with western blot. Overall, we illustrated that myristicin could regulate apoptosis signaling pathways in MCF-7 BC cells.

摘要

本研究主要关注肉豆蔻醚对 MCF-7 人乳腺癌(BC)细胞的抗癌活性。BC 是全球女性中最常见和主要的恶性疾病。如今,各种常规疗法被用于治疗 BC,但仍然是一个主要挑战,因为这些治疗方法无法区分正常细胞和恶性细胞,而且它们也有严重的副作用。因此,需要开发新的疗法来降低与 BC 相关的发病率和死亡率。肉豆蔻醚,一种 1-丙烯基-5-甲氧基-3,4-亚甲基二氧基苯,是存在于各种香料中的主要活性芳香化合物,如肉豆蔻、肉豆蔻衣、胡萝卜、肉桂、欧芹和一些精油。肉豆蔻醚具有广泛的作用,包括抗肿瘤、抗氧化和抗菌活性。然而,肉豆蔻醚对人 BC 细胞的影响在很大程度上仍未被揭示。通过(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐和乳酸脱氢酶测定法检测到肉豆蔻醚对 MCF-7 细胞的细胞毒性作用呈剂量依赖性增加。与对照组相比,吖啶橙/溴化乙锭、Hoechst 染色和 Annexin V 检测发现肉豆蔻醚能显著诱导细胞凋亡。此外,它还能激活细胞抗迁移、细胞内活性氧的产生和细胞周期在 G/S 期的停滞。此外,通过定量聚合酶链反应证实,肉豆蔻醚诱导凋亡和细胞周期基因(Caspases8、Bax、Bid、Bcl2、PARP、p53 和 Cdk1)的表达,并通过 Western blot 分析凋亡蛋白(c-PARP、Caspase 9、细胞色素 C、PDI)的表达。总的来说,我们表明肉豆蔻醚可以调节 MCF-7 BC 细胞中的凋亡信号通路。

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