关键词: DNA damage alantolactone apoptosis cell cycle cervical cancer

Mesh : Humans Animals Ataxia Telangiectasia Mutated Proteins / metabolism Uterine Cervical Neoplasms / drug therapy pathology metabolism Apoptosis / drug effects Female Checkpoint Kinase 2 / metabolism Mice, Nude DNA Damage / drug effects Signal Transduction / drug effects Sesquiterpenes, Eudesmane / pharmacology therapeutic use Lactones / pharmacology therapeutic use HeLa Cells Cell Proliferation / drug effects Antineoplastic Agents, Phytogenic / pharmacology therapeutic use Cell Line, Tumor Xenograft Model Antitumor Assays Mice, Inbred BALB C Mice Inula / chemistry

来  源:   DOI:10.1248/bpb.b23-00804

Abstract:
Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT\'s anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT\'s effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.
摘要:
中药,以其最小的副作用和显著的临床疗效而闻名,它在癌症治疗中的潜力引起了相当大的兴趣。特别是,InulaheleniumL.已证明在抑制多种癌症方面有效。这项研究的重点是alantolactone(ALT),一种来自InulaheleniumL.的突出化合物,因其在多种癌症类型中的抗癌能力而获得认可。这项研究的主要目的是检查ALT对增殖的影响,凋亡,细胞周期,和宫颈癌(CC)细胞的肿瘤生长,及其相关的信号通路。为了确定蛋白质表达改变,进行蛋白质印迹分析。此外,通过将HeLa细胞皮下注射到裸鼠体内建立体内模型,以评估ALT对宫颈癌的影响.我们的研究彻底调查了CC背景下ALT的抗肿瘤潜力。发现ALT在SiHa和HeLa细胞系中抑制细胞增殖并诱导细胞凋亡,特别是针对与DNA损伤相关的共济失调-毛细血管扩张突变(ATM)蛋白。当ATM被抑制时,DNA损伤的抑制和细胞凋亡的诱导强调了ATM/细胞周期检查点激酶2(CHK2)轴在ALT抗肿瘤作用中的关键作用。用异种移植小鼠模型进行的体内研究进一步验证了ALT在减少CC肿瘤生长和促进细胞凋亡方面的有效性。这项研究提供了关于ALT如何对抗CC的新见解,强调其作为一种有效的抗宫颈癌药物的前景,并为改善CC患者的治疗结果提供希望。
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