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干细胞提取物对H838人非小细胞肺癌细胞以及RPA32、弹性蛋白酶、酪氨酸酶和透明质酸酶蛋白的细胞毒性和多酶抑制作用

Cytotoxicity and Multi-Enzyme Inhibition of Stem Extract on H838 Human Non-Small Cell Lung Cancer Cells and RPA32, Elastase, Tyrosinase, and Hyaluronidase Proteins.

作者信息

Lee Ching-Yi, Chen Yu-Cheng, Huang Yen-Hua, Lien Yi, Huang Cheng-Yang

机构信息

Department of Internal Medicine, Tao Yuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan.

Department of Biomedical Sciences, Chung Shan Medical University, Taichung City 402, Taiwan.

出版信息

Plants (Basel). 2024 Mar 11;13(6):797. doi: 10.3390/plants13060797.

Abstract

The carnivorous pitcher plants of the genus have long been known for their ethnobotanical applications. In this study, we prepared various extracts from the pitcher, stem, and leaf of using 100% ethanol and assessed their inhibitory effects on key enzymes related to skin aging, including elastase, tyrosinase, and hyaluronidase. The cytotoxicity of the stem extract of on H838 human lung carcinoma cells were also characterized by effects on cell survival, migration, proliferation, apoptosis induction, and DNA damage. The cytotoxic efficacy of the extract was enhanced when combined with the chemotherapeutic agent 5-fluorouracil (5-FU), indicating a synergistic effect. Flow cytometry analysis suggested that the stem extract might suppress H838 cell proliferation by inducing G2 cell cycle arrest, thereby inhibiting carcinoma cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 15 most abundant compounds in the stem extract of . Notably, the extract showed a potent inhibition of the human RPA32 protein (huRPA32), critical for DNA replication, suggesting a novel mechanism for its anticancer action. Molecular docking studies further substantiated the interaction between the extract and huRPA32, highlighting bioactive compounds, especially the two most abundant constituents, stigmast-5-en-3-ol and plumbagin, as potential inhibitors of huRPA32's DNA-binding activity, offering promising avenues for cancer therapy. Overall, our findings position the stem extract of as a promising source of natural compounds for anticancer therapeutics and anti-skin-aging treatments, warranting further investigation into its molecular mechanisms and potential clinical applications.

摘要

猪笼草属的食肉猪笼草长期以来因其民族植物学应用而闻名。在本研究中,我们使用100%乙醇从猪笼草的捕虫笼、茎和叶中制备了各种提取物,并评估了它们对与皮肤老化相关的关键酶(包括弹性蛋白酶、酪氨酸酶和透明质酸酶)的抑制作用。猪笼草茎提取物对H838人肺癌细胞的细胞毒性还通过对细胞存活、迁移、增殖、凋亡诱导和DNA损伤的影响来表征。当与化疗药物5-氟尿嘧啶(5-FU)联合使用时,提取物的细胞毒性功效增强,表明存在协同作用。流式细胞术分析表明,茎提取物可能通过诱导G2期细胞周期停滞来抑制H838细胞增殖,从而抑制癌细胞增殖。气相色谱-质谱联用(GC-MS)能够初步鉴定猪笼草茎提取物中15种最丰富的化合物。值得注意的是,该提取物对DNA复制至关重要的人类RPA32蛋白(huRPA32)表现出强烈抑制作用,这表明了其抗癌作用的新机制。分子对接研究进一步证实了提取物与huRPA32之间的相互作用,突出了生物活性化合物,特别是两种最丰富的成分,豆甾-5-烯-3-醇和白花丹素,作为huRPA32 DNA结合活性的潜在抑制剂,为癌症治疗提供了有希望的途径。总体而言,我们的研究结果表明猪笼草茎提取物是抗癌治疗和抗皮肤老化治疗天然化合物的有希望来源,值得进一步研究其分子机制和潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5c/10974603/dc5e36dab878/plants-13-00797-g001.jpg

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