Department of Tea Science, Zhejiang University, Hangzhou 310058, China.
College of Health, Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.
Molecules. 2020 Jul 31;25(15):3515. doi: 10.3390/molecules25153515.
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.
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。