Phuong Anh Nguyen, Yun-Suk Kwon, Nam-Yi Kim, Munseon Lee, In Hyun Hwang, Soyoung Kim
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Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor-bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. 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引用次数: 0
摘要
放射抗药性是癌症治疗的一大障碍。莲子提取物(LSE)已在多种癌细胞中显示出抗癌效果。然而,它对抗辐射肿瘤的潜力仍不清楚。在本研究中,我们旨在研究莲子心提取物对放射线耐药性乳腺癌细胞的作用,探索其潜在机制,并确定其细胞毒性作用的主要成分。用 70% 乙醇提取的 LSE 与亲代细胞相比,对放射线耐受性乳腺癌细胞具有选择性细胞毒性作用。通过化学分析发现,槲皮素及其衍生物金丝桃苷和米槲皮苷是产生这些选择性效应的主要成分。值得注意的是,与金丝桃苷和米桔皮苷相比,槲皮素对放射抗性乳腺癌细胞的细胞毒性最强。进一步研究发现,这些化合物抑制了 DNA 修复系统的激活,从而导致 DNA 损伤的积累并诱导细胞凋亡。重要的是,它们能有效抑制 ACSL4 的表达,而 ACSL4 是以前与放射抗性相关的一个因子。在一项体内研究中,槲皮素能显著抑制耐放射性肿瘤小鼠的肿瘤生长。综上所述,我们的研究结果凸显了 LSE 及其主要成分槲皮素及其衍生物在克服乳腺癌放射抗性方面的潜力。这项研究提供了令人信服的证据,支持将 LSE 用作未来对抗乳腺癌放射抗性的辅助疗法的药源。
Quercetin and its derivatives from lotus (Nelumbo nucifera) seedpod extract combat radioresistance by suppressing ACSL4.
Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor-bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers.
期刊介绍:
BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease.
The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements.
In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.