赤芝（Ganoderma calidophilum）代表了灵芝属中的一个独特品种，被土著黎族用作预防和治疗癌症的药物。然而，G. calidophilum 在抗肿瘤治疗中的精确生物活性和作用在很大程度上仍未得到解决。已从 G. calidophilum 中分离出几种羊毛甾烷三萜类化合物。酶活性分析表明，四种羊毛甾烷三萜类化合物表现出 PTP1B 抑制活性，对 SHP2、SHP1、PTPN5、PTPRA、STEP 和 TCPTP 的抑制最小。分子对接分析表明这些化合物主要与 PTP1B 的底物识别和进入区域结合。进一步分析表明，其中灵芝醛A（GAA）是一种选择性、非竞争性的PTP1B抑制剂。 GAA 以剂量依赖性方式抑制 C33A 和 MDA-MB-231 细胞的增殖、集落形成和迁移。 GAA 具有以细胞类型特异性方式诱导细胞凋亡的能力，无论是依赖于半胱天冬酶还是不依赖于半胱天冬酶。 PTP1B siRNA 显着降低 GAA 的细胞毒性作用，而 PTP1B 的过表达显着增加 GAA 处理后的细胞生长。这些发现证实 PTP1B 是 GAA 的功能靶点。 GAA作用机制的研究表明，它可以通过抑制PTP1B来抑制AKT的激活，同时激活p38，从而促进细胞死亡。基于羊毛甾醇三萜骨架开发特异性PTP1B抑制剂是可能的。 G. calidophilum 有潜力被开发成功能性食品或药物，以预防和治疗癌症。版权所有 © 2024 Elsevier B.V. 保留所有权利。

The species Ganoderma calidophilum represents a distinct variety within the genus Ganoderma and used by the indigenous Li ethnic group as a medicinal agent for the prevention and treatment of cancer. However, the precise biological activity and role of G. calidophilum in antitumor treatment remain largely unresolved. Several lanostane triterpenoids have been isolated from G. calidophilum. The enzyme activity analysis revealed that four lanostane triterpenoids exhibited PTP1B inhibition activity, with minimal inhibition towards SHP2, SHP1, PTPN5, PTPRA, STEP and TCPTP. Molecular docking analysis demonstrated that these compounds primarily bind to the substrate recognition and entry regions of PTP1B. Further analysis indicated that among them, ganoderic aldehyde A (GAA) is a selective and non-competitive PTP1B inhibitor. GAA inhibited the proliferation, colony formation and migration of C33A and MDA-MB-231 cells in a dose-dependent manner. GAA has the capacity to induce apoptosis in a cell-type-specific manner, both in a caspase-dependent and -independent manner. PTP1B siRNA significantly reduced the cytotoxic effect of GAA, while overexpression of PTP1B significantly increased cell growth after GAA treatment. These findings confirm that PTP1B is a functional target of GAA. Research into the mechanisms of action of GAA has revealed that it could inhibit the activation of AKT by inhibiting PTP1B, while simultaneously activating p38, which promotes cell death. It is possible to develop specific PTP1B inhibitors based on the lanosterol triterpene skeleton. G. calidophilum has the potential to be developed into functional foods or drugs with the aim of preventing and treating cancer.Copyright © 2024 Elsevier B.V. All rights reserved.