Priyadarshini Arpita, Mohanty Debajani, Mohanty Swagat, Kerry Rout George, Sahoo Ambika, Dash Biswabhusan, Panda Pratap Chandra, Nayak Sanghamitra, Ray Asit, Jena Sudipta
Centre for Biotechnology, Siksha O Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar, 751003, India.
Sci Rep. 2025 Jul 9;15(1):24739. doi: 10.1038/s41598-025-10761-0.
Prostate cancer (PCa), a common urinary malignancy, is the leading cause of mortality and morbidity among men worldwide. Curcuma amada extract has demonstrated antitumor properties in preclinical models of various cancers, however, its mechanisms against prostate cancer remain unclear. The current study aims to investigate the underlying mechanism of C. amada rhizome extract (CARE) in treating PCa through network pharmacology, bioinformatics analysis and in-vitro experiments. UHPLC-QTOF-HRMS/MS detected 16 phytoconstituents in C. amada, with 15 constituents passing drug-likeness criteria. Public databases identified 1,311 CARE and 473 PCa related targets, with 59 overlapping targets. PPI analysis revealed P53, CTNNB1, EGFR, AKT1, ESR1, HIF1A, CCND1, PIK3CA, and BCL2 as hub targets. Further,4-hydroxycinnamic acid, 13-hydroxylabda-8(17),14-dien-18-oic acid, labda-8(17),12-diene-15,16-dial, zederone, zedoarondiol, zerumin A and caffeic acid were identified as core compounds with high degree values. GO and KEGG analysis identified targets primarily associated with apoptosis and PI3K-AKT signalling pathway. Molecular docking confirmed good binding potential of core compounds with key hub targets, while molecular dynamics (MD) simulation validated the stability of these interactions with minimal fluctuations throughout the simulation. Additionally, mRNA expression levels, immune infiltration and genetic alteration of the hub targets were analyzed. CARE significantly inhibited the proliferation of PC-3 cells, induced apoptosis, and caused G2/M phase arrest. In addition, qRT-PCR analysis revealed that CARE was able to suppress mRNA expression of genes involved in the PI3K-AKT signalling pathway. Thus, the study highlights the underlying mechanism of CARE as a promising treatment option for prostate cancer.
前列腺癌（PCa）是一种常见的泌尿系统恶性肿瘤，是全球男性死亡和发病的主要原因。莪术提取物在各种癌症的临床前模型中已显示出抗肿瘤特性，然而，其抗前列腺癌的机制仍不清楚。本研究旨在通过网络药理学、生物信息学分析和体外实验，探讨莪术根茎提取物（CARE）治疗PCa的潜在机制。超高效液相色谱-四极杆飞行时间-高分辨质谱联用仪（UHPLC-QTOF-HRMS/MS）检测到莪术中的16种植物成分，其中15种成分符合类药标准。公共数据库确定了1311个CARE相关靶点和473个PCa相关靶点，有59个重叠靶点。蛋白质-蛋白质相互作用（PPI）分析显示P53、β-连环蛋白（CTNNB1）、表皮生长因子受体（EGFR）及蛋白激酶B（AKT1）、雌激素受体1（ESR1）、缺氧诱导因子1α（HIF1A）、细胞周期蛋白D1（CCND1）、磷脂酰肌醇-3激酶催化亚基α（PIK3CA）和B细胞淋巴瘤/白血病-2（BCL2）为枢纽靶点。此外，4-羟基肉桂酸、13-羟基-8（17），14-二烯-18-酸、8（17），12-二烯-15，16-二醛、姜黄酮、莪术二醇、莪术酮A和咖啡酸被确定为具有高度数值的核心化合物。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析确定靶点主要与细胞凋亡和PI3K-AKT信号通路相关。分子对接证实了核心化合物与关键枢纽靶点具有良好的结合潜力，而分子动力学（MD）模拟验证了这些相互作用在整个模拟过程中的稳定性，波动极小。此外，还分析了枢纽靶点的mRNA表达水平、免疫浸润和基因改变情况。CARE显著抑制PC-3细胞的增殖，诱导细胞凋亡，并导致G2/M期阻滞。此外，实时定量聚合酶链反应（qRT-PCR）分析显示，CARE能够抑制PI3K-AKT信号通路相关基因的mRNA表达。因此，本研究突出了CARE作为前列腺癌一种有前景的治疗选择的潜在机制。
