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肿瘤抑制基因 p53 (TP53)，它与 ​​OSCC 患者的较低生存率和治疗抵抗力有关。落新妇苷是多种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。本研究评估了落新妇苷对 OSCC 细胞系 SCC90 和 SCC4（带有 p53 突变）增殖的影响（与 p53 和 Mdm-2 通路相关）。落新妇苷以剂量和时间依赖性方式抑制SCC4和SCC90细胞的增殖。两种细胞系的落新妇苷的 IC50 值约为 75 μM。使用 p53 激活剂 (RITA) 测定落新妇苷对 p53 活性的影响，结果表明可协同减少细胞生长。然而，当与pifithrin-α（一种p53抑制剂）联合使用时，落新妇苷对其反应表现出强烈的抑制作用。落新妇苷降低了 SCC4 细胞中的线粒体膜电位，这是细胞凋亡活性的标志。 Astilbin 降低了 Mdm-2（p53 负调节因子）的含量，并增加了 p53 基因和蛋白质的表达。以 p53 依赖性方式，落新妇苷抑制 SCC4 细胞形成集落和愈合伤口的能力。随后通过激活 caspase 9 和 3、切割 PARP 以及抑制促凋亡 Bid 来诱导线粒体内在凋亡。作为草药成分，落新妇苷诱导 OSCC 细胞中 p53 介导的细胞凋亡。© 2024。Pleiades Publishing, Ltd.

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.© 2024. Pleiades Publishing, Ltd.