Ganoderic acid T, a Ganoderma triterpenoid, modulates the tumor microenvironment and enhances the chemotherapy and immunotherapy efficacy through downregulating galectin-1 levels.

Autor: Chen S; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Chen K; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Lin Y; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Wang S; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Yu H; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Chang C; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Cheng T; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Hsieh C; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Li J; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Lai H; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan., Chen D; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan. Electronic address: salaben0624@gmail.com., Huang C; Trineo Biotechnology Co., Ltd, 20F, No.81, Sec.1, Xintai 5th Rd, Xizhi Dist., New Taipei City 221, Taiwan. Electronic address: cphuang1978@gmail.com.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Oct; Vol. 491, pp. 117069. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1016/j.taap.2024.117069
Abstrakt: Ganoderic acid T (GAT), a triterpenoid molecule of Ganoderma lucidum, exhibits anti-cancer activity; however, the underlying mechanisms remain unclear. Therefore, in this study, we aimed to investigate the anti-cancer molecular mechanisms of GAT and explore its therapeutic applications for cancer treatment. GAT exhibited potent anti-cancer activity in an ES-2 orthotopic ovarian cancer model in a humanized mouse model, leading to significant alterations in the tumor microenvironment (TME). Specifically, GAT reduced the proportion of α-SMA + cells and enhanced the infiltration of tumor-infiltrating lymphocytes (TILs) in tumor tissues. After conducting proteomic analysis, it was revealed that GAT downregulates galectin-1 (Gal-1), a key molecule in the TME. This downregulation has been confirmed in multiple cancer cell lines and xenograft tumors. Molecular docking suggested a theoretical direct interaction between GAT and Gal-1. Further research revealed that GAT induces ubiquitination of Gal-1. Moreover, GAT significantly augmented the anti-cancer effects of paclitaxel, thereby increasing intratumoral drug concentrations and reducing tumor size. Combined with immunotherapy, GAT enhanced the tumor-suppressive effects of the anti-programmed death-ligand 1 antibody and increased the proportion of CD8 + cells in the EMT6 syngeneic mammary cancer model. In conclusion, GAT inhibited tumor growth, downregulated Gal-1, modulated the TME, and promoted chemotherapy and immunotherapy efficacy. Our findings highlight the potential of GAT as an effective therapeutic agent for cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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