Batool Zahra, Wu Qihang, Kamal Mohammad Amjad, Weng Guobin, Shen Bairong
Department of Urology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital Sichuan University Chengdu China.
Department of Food Science Huazhong Agriculture University Wuhan China.
Food Sci Nutr. 2025 Jul 16;13(7):e70442. doi: 10.1002/fsn3.70442. eCollection 2025 Jul.
Renal carcinoma is a lethal cancer, researched by several studies to get insights into the molecular causes of disease, in order to come up with advanced therapeutic treatments. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is an anticancer cytokine posing therapeutic effects to treat cancer. However, certain cancer types including renal cell carcinoma developed resistance towards TRAIL, hence limiting its usefulness in cancer treatment. Recently, synergistic approach has been emerged in clinical settings to sensitize cancer cells towards TRAIL treatment by combining with natural antioxidants and anti-inflammatory compounds for providing chemo-sensitizing effects. Hence, this study has used chemo-sensitizing effect of chrysoeriol for the very first time to sensitize renal carcinoma cell lines for treatment with TRAIL by synergistic treatment approach, in vitro. The effects of 20 μM chrysoeriol, 50 ng/mL TRIAL and their synergistic combination were investigated deeply by adopting different experimental strategies in vitro. Synergistic combination of 20 μM chrysoeriol/50 ng/mL TRIAL provided apoptosis of TRAIL resistant cell lines which was confirmed by increasing the expressions of caspases including caspase-3 and caspase-8 and caspase-9, increasing the expression of interleukins 10, while decreasing the expression of interleukins 6, triggering cellular apoptosis, inhibiting proteasome activity, lossing mitochondrial membrane potential and triggering cytchrome C release. Meanwhile, rise in death receptor 4 expression as well as up-regulation of pro-apoptotic and down-regulation of anti-apoptotic genes further provided evidence for chemo-sensitizing effect of chrysoeriol on TRAIL resistant renal carcinoma cells to trigger apoptosis. Hence, chrysoeriol could be employed in the anticancer drug development for therapeutic treatment of renal cancer.
肾癌是一种致命的癌症，多项研究对其进行了探究，以深入了解疾病的分子病因，从而研发出先进的治疗方法。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种具有抗癌作用的细胞因子，可用于治疗癌症。然而，包括肾细胞癌在内的某些癌症类型对TRAIL产生了耐药性，因此限制了其在癌症治疗中的应用。最近，临床中出现了一种协同方法，即通过与天然抗氧化剂和抗炎化合物联合使用，使癌细胞对TRAIL治疗敏感，从而产生化学增敏作用。因此，本研究首次利用白杨素的化学增敏作用，通过体外协同治疗方法使肾癌细胞系对TRAIL治疗敏感。采用不同的体外实验策略，深入研究了20μM白杨素、50 ng/mL TRAIL及其协同组合的效果。20μM白杨素/50 ng/mL TRAIL的协同组合可诱导TRAIL耐药细胞系凋亡，这通过增加包括caspase-3、caspase-8和caspase-9在内的半胱天冬酶表达、增加白细胞介素10的表达、降低白细胞介素6的表达、触发细胞凋亡、抑制蛋白酶体活性、降低线粒体膜电位和触发细胞色素C释放得以证实。同时，死亡受体4表达的增加以及促凋亡基因的上调和抗凋亡基因的下调，进一步证明了白杨素对TRAIL耐药肾癌细胞的化学增敏作用可触发细胞凋亡。因此，白杨素可用于抗癌药物研发，以治疗肾癌。
