College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; College of Life Sciences, Westlake University, Hangzhou 310058, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 6):127429. doi: 10.1016/j.ijbiomac.2023.127429. Epub 2023 Oct 12.
Colon cancer, a prevalent malignant tumor affecting the digestive system, presents a substantial risk to human health due to its high occurrence and mortality rates. Phellinus baumii polyphenol (PBP), a natural product derived from traditional Chinese medicine, has gained widespread popularity due to its low toxicity and minimal side effects, compared to radiation and chemotherapy. This study used an integrated approach of network pharmacology and experimental verification to elucidate the anti-colon cancer effects of PBP and its potential mechanisms. In network pharmacology, the identification of relevant targets involved a comprehensive search across multiple databases using keywords such as "active components of PBP" and "colon cancer". Venn diagram analysis was subsequently performed to ascertain the shared targets. To identify the key active components and core targets, we constructed a network of "Disease-Drug-Pathways-Targets" and a protein-protein interaction (PPI) network among the targets using Cytoscape 3.9.1. Furthermore, molecular docking was carried out to predict the binding affinity and conformation between the main active compounds (davallialactone and citrinin) of PBP and the core targets (TP53, STAT3, CASP3, CTNNB1, PARP1, MYC). To validate our findings, in vitro experiments were conducted. We verified that PBP exerted an anti-colon cancer effect on human colon cancer HCT116 cells by significantly inhibiting cell proliferation, promoting apoptosis and arresting the cell cycle in S phase by using Cell Counting Kit-8 (CCK-8) and flow cytometry. Finally, we determined the key regulatory proteins related to apoptosis and the cell cycle by western blot analysis, and proposed the potential mechanism by which PBP exerts an anti-colon cancer effect by inducing the caspase-dependent mitochondrial-mediated intrinsic apoptotic pathway and arresting the cell cycle in S phase in HCT116 cells. These results suggest that PBP possesses substantial potential for the treatment of colon cancer and may serve as a viable alternative therapeutic strategy in colon cancer treatment.
结直肠癌是一种常见的消化系统恶性肿瘤，其发病率和死亡率较高，严重威胁人类健康。桑黄多酚（PBP）是一种从传统中药中提取的天然产物，与放疗和化疗相比，其毒性低、副作用小，因此受到广泛关注。本研究采用网络药理学和实验验证相结合的方法，阐明 PBP 抗结肠癌的作用及其潜在机制。在网络药理学中，通过使用“PBP 的活性成分”和“结肠癌”等关键词，全面搜索多个数据库，以确定相关靶点。然后进行 Venn 图分析，以确定共享靶点。为了确定关键的活性成分和核心靶点，我们使用 Cytoscape 3.9.1 构建了“疾病-药物-途径-靶点”网络和靶点之间的蛋白质-蛋白质相互作用（PPI）网络。此外，通过分子对接预测 PBP 的主要活性化合物（白头翁内酯和桔霉素）与核心靶点（TP53、STAT3、CASP3、CTNNB1、PARP1、MYC）之间的结合亲和力和构象。为了验证我们的研究结果，进行了体外实验。我们通过 CCK-8 和流式细胞术证实，PBP 对人结肠癌 HCT116 细胞的增殖具有显著的抑制作用，能够促进细胞凋亡并将细胞周期阻滞在 S 期。最后，通过 Western blot 分析确定了与细胞凋亡和细胞周期相关的关键调节蛋白，并提出了 PBP 通过诱导 caspase 依赖性线粒体介导的内在凋亡途径和阻滞 HCT116 细胞周期在 S 期发挥抗结肠癌作用的潜在机制。这些结果表明 PBP 具有治疗结肠癌的巨大潜力，可能成为结肠癌治疗的一种可行的替代治疗策略。
