Lanostane triterpenoids from Ganoderma calidophilum exhibit potent anti-tumor activity by inhibiting PTP1B
文献类型： 外文期刊
作者： Chen, Chuan 1 ; Xu, Ruixuan 1 ; Guo, Chenxiao 1 ; Li, Xiangke 1 ; Zhao, Youxing 4 ; Luo, Duqiang 1 ;
作者机构： 1.Hebei Univ, Coll Life Sci, Baoding 071002, Hebei, Peoples R China
2.Hebei Univ, Key Lab Microbial Divers Res & Applicat Hebei Prov, Baoding 071002, Hebei, Peoples R China
3.Hebei Univ, Hebei Innovat Ctr Bioengn & Biotechnol, Baoding 071002, Peoples R China
4.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Key Lab Res & Dev Nat Prod Li Folk Med Hainan Prov, Haikou 571101, Peoples R China
5.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Natl Key Lab Trop Crop Breeding, Haikou 571101, Peoples R China
关键词： Triterpenoid; Ganoderma calidophilum; Cancer; PTP1B; Apoptosis
期刊名称：CHEMICO-BIOLOGICAL INTERACTIONS （ 影响因子：5.4； 五年影响因子：5.1 ）
ISSN： 0009-2797
年卷期： 2024 年 403 卷
页码：
收录情况： SCI
摘要： 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.
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