Inonotus hispidus（I. hispidus），被称为毛头菇，一直被广泛用于中国和一些东亚国家作为传统药用大型真菌，用于治疗诸如糖尿病、痛风和关节炎等疾病。现代药理学研究表明，I. hispidus在抗肿瘤治疗中具有重要的应用价值。但是，其菌丝体中的主要抗宫颈癌活性物质及其作用机制仍不清楚。为了丰富I. hispidus的种质资源，揭示I. hispidus菌丝提取物对宫颈癌的抗肿瘤活性，并初步分析其作用机制。SH3菌株是从野生子实体中分离出的，并通过形态和分子生物学鉴定。利用液相色谱-串联质谱技术分离和鉴定了I. hispidus菌丝体中的抗肿瘤活性成分。采用MTT法评估了细胞活性。通过流式细胞仪检测细胞周期分布、凋亡细胞检测和线粒体膜电位。通过Western blot检测凋亡相关蛋白的表达。通过小鼠异种移植模型评估肿瘤生长的抑制。SH3菌株被分离并鉴定为I. hispidus新菌株。首次分离了菌丝体中含有环肽的抗肿瘤活性成分（CCM）。此外，我们发现CCM对HeLa增殖具有强烈的抑制作用，无论是在体内还是体外。机械地说，CCM阻止了细胞周期处于G0/G1期，降低了线粒体膜电位，最终通过上调Bax、细胞色素C、裂解的caspase-9和裂解的caspase-3的表达水平和下调Bcl-2的表达水平，促进了线粒体介导的HeLa细胞凋亡。我们的研究不仅丰富了I. hispidus的菌株资源，而且证实了该菌株的菌丝体具有抑制宫颈癌的活性成分。这对于开发用于治疗宫颈癌的活性药物和药物引导分子具有重要意义。版权所有©2023 Elsevier B.V.出版。

Inonotus hispidus (I. hispidus), known as shaggy bracket, has been used extensively in China and some East Asian countries as a traditional medicinal macrofungus to treat difficult diseases, such as diabetes, gout, and arthritis. Modern pharmacological research has shown that I. hispidus has an important application value in antitumor treatment. However, the main anti-cervical cancer activity substances from its mycelia and its mechanisms are still not clear.To enrich the germplasm resources of I. hispidus, to reveal the antitumor activity of the extract from the mycelium of I. hispidus against cervical cancer, and to preliminarily analyze its action mechanism.The SH3 strain was isolated from wild fruiting bodies and identified by morphology and molecular biology. The antitumor active component from the mycelium of I. hispidus was isolated and identified with liquid chromatography-tandem mass spectrometry. The cell viability was assessed by MTT assay. The cell cycle distribution, apoptotic cell detection, and mitochondrial membrane potential were detected by flow cytometer. The expression of apoptosis-related proteins was assessed by Western blotting. The inhibition of tumor growth in vivo was assessed by a mouse xenograft model.The SH3 strain was isolated and identified as a new strain of I. hispidus. The antitumor active component containing cyclic peptides from the mycelium of I. hispidus (CCM) was isolated for the first time. In addition, we found that CCM had a strong inhibitory effect on HeLa proliferation in vitro and in vivo. Mechanically, the CCM blocked the cell cycle at the G0/G1 phase, decreased the mitochondrial membrane potential, and eventually promoted apoptosis of HeLa cells through the mitochondria-mediated pathway by upregulating the expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3 and downregulating the expression level of Bcl-2.Our study not only enriches the strain resources of I. hispidus but also confirms that the mycelium of this strain has active components that can inhibit cervical cancer. This is highly significant for the development of active drugs and drug lead molecules for treating cervical cancer.Copyright © 2023. Published by Elsevier B.V.