Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aimin Wu, Chungang Zhao
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引用次数: 0

Abstract

Oral squamous cell carcinoma (OSCC) is a frequently occurring malignancy in the head and neck region. The most commonly mutated gene in OSCC is the tumor suppressor gene p53 (TP53), linked to lower survival and treatment resistance in OSCC patients. Astilbin is a flavonoid amongst several herbal treatments with a variety of pharmacological actions mainly including antioxidant, anti-inflammatory, and anti-cancer characteristics. This study evaluated the effects of astilbin on proliferation of OSCC cell lines SCC90 and SCC4 (bearing a p53 mutation) in relevance to p53 and Mdm-2 pathways. Astilbin inhibited the proliferation of SCC4 and SCC90 cells in a dose- and time-dependent manner. The IC50 values for both the cell lines were about 75 μM for astilbin. A p53 activator (RITA) was used to determine the effects of astilbin on p53 activity, and the results demonstrated synergistic reduction in cell growth. However, when combined with pifithrin-α (a p53 inhibitor), astilbin demonstrated a strong inhibition of its response. Astilbin reduced the mitochondrial membrane potential in SCC4 cells, which is a sign of apoptotic activity. Astilbin decreased the amounts of Mdm-2 (negative regulator of p53) and increased the expression of the p53 gene and protein. In a p53-dependent manner, astilbin suppressed the ability of SCC4 cells to form colonies and heal wounds. This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients.

Abstract Image

Abstract Image

阿斯替滨通过 p53 重激活和 Mdm-2 抑制诱导口腔鳞状细胞癌细胞凋亡
口腔鳞状细胞癌(OSCC)是头颈部常见的恶性肿瘤。OSCC中最常见的突变基因是抑癌基因p53(TP53),它与OSCC患者的低生存率和耐药性有关。黄芪是多种中草药中的一种黄酮类化合物,具有多种药理作用,主要包括抗氧化、抗炎和抗癌特性。本研究评估了天人菊素对 OSCC 细胞株 SCC90 和 SCC4(带有 p53 突变)增殖的影响,这与 p53 和 Mdm-2 通路有关。芪蛭素以剂量和时间依赖性的方式抑制了SCC4和SCC90细胞的增殖。两种细胞株的芪醇素 IC50 值均为 75 μM 左右。为了确定芪蛭素对 p53 活性的影响,我们使用了一种 p53 激活剂(RITA)。然而,当与 pifithrin-α(一种 p53 抑制剂)结合使用时,芪蛭素会对其反应产生强烈的抑制作用。芪醇素降低了 SCC4 细胞的线粒体膜电位,而线粒体膜电位是细胞凋亡的标志。芪醇素降低了 Mdm-2(p53 的负调控因子)的含量,并增加了 p53 基因和蛋白的表达。通过 p53 依赖性方式,芪醇素抑制了 SCC4 细胞形成菌落和愈合伤口的能力。随后,通过激活 caspases 9 和 3、PARP 的裂解以及抑制促凋亡 Bid,诱导线粒体内在凋亡。作为中药成分,天人菊素诱导 p53 介导的 OSCC 细胞凋亡。
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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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