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百粤 1 号茶花标准化总皂苷通过 AKT-MDM2-p53 信号通路诱导卵巢癌细胞 S 期细胞周期阻滞和凋亡。

Standardized Saponin Extract from Baiye No.1 Tea () Flowers Induced S Phase Cell Cycle Arrest and Apoptosis via AKT-MDM2-p53 Signaling Pathway in Ovarian Cancer Cells.

机构信息

Department of Tea Science, Zhejiang University, Hangzhou 310058, China.

College of Health, Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.

出版信息

Molecules. 2020 Jul 31;25(15):3515. doi: 10.3390/molecules25153515.

DOI:10.3390/molecules25153515
PMID:32752095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7435957/
Abstract

Ovarian cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anti-cancer agents. Saponins are characteristic components of tea () flower and have various biological activities, including anti-tumor effects. In this study, a high purity standardized saponin extract, namely Baiye No.1 tea flower saponin (BTFS), which contained Floratheasaponin A and Floratheasaponin D, were isolated from tea ( cv. Baiye 1) flowers by macroporous resin and preparative liquid chromatography. Then, the component and purity were detected by UPLC-Q-TOF/MS/MS. This high purity BTFS inhibited the proliferation of A2780/CP70 cancer cells dose-dependently, which is evidenced by the inhibition of cell viability, reduction of colony formation ability, and suppression of PCNA protein expression. Further research found BTFS induced S phase cell cycle arrest by up-regulating p21 proteins expression and down-regulating Cyclin A2, CDK2, and Cdc25A protein expression. Furthermore, BTFS caused DNA damage and activated the ATM-Chk2 signaling pathway to block cell cycle progression. Moreover, BTFS trigged both extrinsic and intrinsic apoptosis-BTFS up-regulated the expression of death receptor pathway-related proteins DR5, Fas, and FADD and increased the ratio of pro-apoptotic/anti-apoptotic proteins of the Bcl-2 family. BTFS-induced apoptosis seems to be related to the AKT-MDM2-p53 signaling pathway. In summary, our results demonstrate that BTFS has the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.

摘要

卵巢癌被认为是女性最严重的恶性肿瘤之一。天然化合物一直被认为是寻找新抗癌药物的重要来源。皂苷是茶花的特征成分,具有多种生物活性,包括抗肿瘤作用。本研究从茶花(cv. Baiye 1)中分离出一种高纯度标准化皂苷提取物,即白花一号茶花花皂苷(BTFS),其包含 Floratheasaponin A 和 Floratheasaponin D。采用大孔树脂和制备液相色谱法从茶花中分离得到。然后,通过 UPLC-Q-TOF/MS/MS 检测其成分和纯度。该高纯度 BTFS 呈剂量依赖性抑制 A2780/CP70 癌细胞的增殖,表现为细胞活力抑制、集落形成能力降低和 PCNA 蛋白表达抑制。进一步研究发现,BTFS 通过上调 p21 蛋白表达和下调 Cyclin A2、CDK2 和 Cdc25A 蛋白表达,诱导 S 期细胞周期停滞。此外,BTFS 引起 DNA 损伤并激活 ATM-Chk2 信号通路以阻止细胞周期进程。此外,BTFS 触发细胞凋亡的内外源性途径-BTFS 上调了死亡受体途径相关蛋白 DR5、Fas 和 FADD 的表达,并增加了 Bcl-2 家族促凋亡/抗凋亡蛋白的比值。BTFS 诱导的细胞凋亡似乎与 AKT-MDM2-p53 信号通路有关。总之,我们的研究结果表明,BTFS 具有作为预防和治疗卵巢癌的营养保健品的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/67a0e18c4647/molecules-25-03515-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/fac90898ebe8/molecules-25-03515-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/935f11de09f1/molecules-25-03515-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/16725489ea24/molecules-25-03515-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/d21c3dd62f1f/molecules-25-03515-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/daeeaf450638/molecules-25-03515-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/bb3d036cfd87/molecules-25-03515-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/67a0e18c4647/molecules-25-03515-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/fac90898ebe8/molecules-25-03515-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/935f11de09f1/molecules-25-03515-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/16725489ea24/molecules-25-03515-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/d21c3dd62f1f/molecules-25-03515-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/daeeaf450638/molecules-25-03515-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/bb3d036cfd87/molecules-25-03515-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/7435957/67a0e18c4647/molecules-25-03515-g007.jpg

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