Silva Lídia Walter de Paula E, Almeida Tamires Cunha, Teixeira Mariane Ster da Silva, Cerrutti Clara Maria Villela, Agostini Lívia da Cunha, Brandão Geraldo Celio, da Silva Glenda Nicioli
School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
Pain and Signaling Laboratory, Butantan Institute, São Paulo, SP, Brazil.
Drug Dev Res. 2025 Nov;86(7):e70172. doi: 10.1002/ddr.70172.
Bladder and ovarian cancers impose a significant burden on healthcare systems due to their high incidence, mortality rates, and the challenges associated with early diagnosis. Current chemotherapy regimens, which typically involve combinations of drugs, often cause severe side effects that negatively impact patient adherence and treatment efficacy. Recently, studies have explored the use of herbal medicines to mitigate the adverse effects of chemotherapy. One such herbal compound is ursolic acid (UA), a triterpene known for its anti-inflammatory, antioxidant, and antitumor properties. This study aimed to evaluate the effects of UA on bladder and ovarian cancer cells harboring TP53 mutations through various assays, including cytotoxicity, clonogenic survival, cell migration, morphological changes, apoptosis, cell cycle analysis, JHDM1D expression and selectivity using MRC-5 cells, along with in silico evaluation. The treatment demonstrated selectivity for tumoral cells and significant antiproliferative effects in both cell types, leading to decreased cell viability, reduced colony-forming ability, inhibited cell migration, morphological changes characteristic of cell death, and increased expression of JHDM1D. In conclusion, UA exhibited antiproliferative activity against bladder and ovarian cancer cell lines with different TP53 mutation sites, suggesting its potential as a promising therapeutic alternative. Moreover, our study demonstrated for the first time the presence of UA in the species F. formosa.
膀胱癌和卵巢癌因其高发病率、死亡率以及早期诊断相关的挑战，给医疗系统带来了沉重负担。目前的化疗方案通常涉及多种药物联合使用，常常会引起严重的副作用，对患者的依从性和治疗效果产生负面影响。最近，研究探索了使用草药来减轻化疗的不良反应。熊果酸（UA）就是这样一种草药化合物，它是一种三萜烯，以其抗炎、抗氧化和抗肿瘤特性而闻名。本研究旨在通过各种试验，包括细胞毒性、克隆形成存活率、细胞迁移、形态变化、凋亡、细胞周期分析、JHDM1D表达以及使用MRC-5细胞进行的选择性评估，以及计算机模拟评估，来评估UA对携带TP53突变的膀胱癌细胞和卵巢癌细胞的影响。该治疗对肿瘤细胞表现出选择性，并对两种细胞类型均具有显著的抗增殖作用，导致细胞活力降低、集落形成能力下降、细胞迁移受到抑制、出现细胞死亡特征性的形态变化以及JHDM1D表达增加。总之，UA对具有不同TP53突变位点的膀胱癌细胞系和卵巢癌细胞系表现出抗增殖活性，表明其作为一种有前景的治疗选择的潜力。此外，我们的研究首次证明了在台湾扁柏中存在UA。
