花青素 3-O-葡萄糖苷在糖异生和氧化应激诱导的癌细胞衰老中的作用机制,Antioxidants

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花青素 3-O-葡萄糖苷在糖异生和氧化应激诱导的癌细胞衰老中的作用机制
Antioxidants ( IF 6.0 ) Pub Date : 2022-04-09 , DOI: 10.3390/antiox11040749
Yaoyao Jia ₁ , Chunyan Wu ₁ , Adriana Rivera-Piza ₁ , Yeon-Ji Kim ₁ , Ji Hae Lee ₁ , Sung-Joon Lee _{1,

2}

Affiliation

Cyanidin-3-O-glucoside (C3G) 是水果和蔬菜中含量丰富的天然花青素，可相互作用并可能调节能量代谢和氧化应激。本研究调查了 C3G 对糖异生和癌细胞衰老的影响。C3G 激活单磷酸腺苷活化蛋白激酶 (AMPK)，这是一种参与新陈代谢和衰老过程的细胞能量传感器。C3G 通过 AMPK 磷酸化灭活 CRTC2 和 HDAC5 共激活因子来降低糖异生基因的表达，从而抑制肝糖异生。C3G 不直接与 AMPK 相互作用，而是通过脂联素受体信号通路激活 AMPK，正如脂联素受体基因敲低实验所证明的那样。此外，C3G 增加了培养的肝细胞中的细胞 AMP 水平，并且在小鼠中口服 C3G 会提高其血浆脂联素浓度。这些作用共同促成了 AMPK 的激活。此外，C3G 显示出有效的抗氧化活性并诱导细胞衰老，并且在氧化应激诱导的肝癌细胞衰老中凋亡。C3G 增加了与衰老相关的 β-半乳糖苷酶的表达，同时增加了细胞衰老的关键标志物 P16、P21 和 P53 的表达水平。这些发现表明，花青素 C3G 通过激活 AMPK 和随后抑制糖异生来实现降血糖作用，并通过诱导细胞凋亡和细胞衰老表现出抗癌活性。此外，C3G 显示出有效的抗氧化活性并诱导细胞衰老，并且在氧化应激诱导的肝癌细胞衰老中凋亡。C3G 增加了与衰老相关的 β-半乳糖苷酶的表达，同时增加了细胞衰老的关键标志物 P16、P21 和 P53 的表达水平。这些发现表明，花青素 C3G 通过激活 AMPK 和随后抑制糖异生来实现降血糖作用，并通过诱导细胞凋亡和细胞衰老表现出抗癌活性。此外，C3G 显示出有效的抗氧化活性并诱导细胞衰老，并且在氧化应激诱导的肝癌细胞衰老中凋亡。C3G 增加了与衰老相关的 β-半乳糖苷酶的表达，同时增加了细胞衰老的关键标志物 P16、P21 和 P53 的表达水平。这些发现表明，花青素 C3G 通过激活 AMPK 和随后抑制糖异生来实现降血糖作用，并通过诱导细胞凋亡和细胞衰老表现出抗癌活性。细胞衰老的关键标志物。这些发现表明，花青素 C3G 通过激活 AMPK 和随后抑制糖异生来实现降血糖作用，并通过诱导细胞凋亡和细胞衰老表现出抗癌活性。细胞衰老的关键标志物。这些发现表明，花青素 C3G 通过激活 AMPK 和随后抑制糖异生来实现降血糖作用，并通过诱导细胞凋亡和细胞衰老表现出抗癌活性。

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Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence

Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knockdown experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated β-galactosidase expression, while increasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence.

更新日期：2022-04-09

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