Department of Pharmacology, Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China.
Central Research Laboratory, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, The Second People's Hospital of Bao'an Shenzhen (Group) Shenzhen, China.
Toxicol Appl Pharmacol. 2022 Nov 1;454:116215. doi: 10.1016/j.taap.2022.116215. Epub 2022 Sep 5.
Breast cancer is a fatal cancer with the highest mortality in female. New strategies for anti-breast cancer are still urgently needed. Catalpol, an iridoid glycoside extracted from the traditional Chinese medicinal plant Rehmannia glutinosa, has shown anticancer efficacy in various cancer cells. However, its effect on breast cancer remains unclear. In this study, we aim to investigate the anti-breast cancer activity of catalpol and elucidate its underlying mechanism. Cell counting kit-8 (CCK-8) and morphology change showed that catalpol could inhibit the proliferation and viability of MCF-7 cells. Catalpol administration reduced the tumor volume in xenograft model. Catalpol induced apoptosis in MCF-7 cells confirmed by Hoechst 33342 staining and Annexin V-FITC/PI double staining. In vivo, catalpol also induced apoptosis as seen from the increased level of terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) in tumor. According to JC-1 and Dichlorodi-hydrofluorescein Diacetate (DCFH-DA) staining, loss of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was found in MCF-7 cells treated with catalpol. Furthermore, catalpol also increased the level of cytoplasmic cytochrome c and activity of caspase-3 in MCF-7 cells. Likewise, histopathological and immunohistochemical (IHC) assay also found that catalpol enhanced the levels of cytochrome c and caspase-3 in breast cancer tissues. Ultimately, acetylation, 2-hydroxyisobutyrylation and lactylation were dramatically increased, whereas succinylation, malonylation and phosphorylation were markedly decreased in the breast cancer tumor treated with catalpol. Taken together, catalpol inhibited breast cancer in vitro and in vivo through induction of apoptosis via mitochondria apoptosis pathway and regulation of protein post-translational modifications (PTMs). Thus, it can be considered as an excellent candidate compound for treatment of breast cancer.
乳腺癌是女性中死亡率最高的致命癌症。仍然迫切需要新的抗乳腺癌策略。梓醇是从传统中药地黄中提取的环烯醚萜苷，已在各种癌细胞中显示出抗癌功效。然而，其对乳腺癌的作用尚不清楚。在这项研究中，我们旨在研究梓醇的抗乳腺癌活性并阐明其潜在机制。细胞计数试剂盒-8（CCK-8）和形态变化表明梓醇可以抑制 MCF-7 细胞的增殖和活力。梓醇给药减少了异种移植模型中的肿瘤体积。Hoechst 33342 染色和 Annexin V-FITC/PI 双重染色证实梓醇诱导 MCF-7 细胞凋亡。体内，从肿瘤中端粒酶介导的缺口末端标记（TUNEL）水平升高也可以看出梓醇诱导了凋亡。根据 JC-1 和二氯二氢荧光素二乙酸酯（DCFH-DA）染色，在梓醇处理的 MCF-7 细胞中发现线粒体膜电位（MMP）丧失和活性氧（ROS）生成。此外，梓醇还增加了 MCF-7 细胞细胞质细胞色素 c 和 caspase-3 的水平。同样，组织病理学和免疫组织化学（IHC）检测还发现梓醇增强了乳腺癌组织中细胞色素 c 和 caspase-3 的水平。最终，梓醇处理的乳腺癌肿瘤中乙酰化、2-羟基异丁酰化和乳酰化显著增加，而琥珀酰化、丙二酰化和磷酸化明显减少。总之，梓醇通过诱导线粒体凋亡途径和调节蛋白质翻译后修饰（PTMs）来抑制体内外乳腺癌。因此，它可以被认为是治疗乳腺癌的优秀候选化合物。
