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- Title
Novel human STING activation by hydrated-prenylated xanthones from Garcinia cowa.
- Authors
Tran, Thi Thu Thuy; Le, Phuong Mai; Nguyen, Thi Kim An; Hoang, Thi Minh Nguyet; Do, Thi Quynh An; Martel, Alexandrine L; Lewicky, Jordan D; Klem, Alexandra; Le, Hoang-Thanh
- Abstract
Objectives: We investigate the anticancer activity and human stimulator of interferon genes pathway activation by a new hydrated-prenylated tetraoxygenated xanthone, garcicowanone I (1) and two known xanthones (2 and 3) that were isolated from the root bark of Garcinia cowa Roxb. ex Choisy. Methods: The anticancer activity of each compound was evaluated by sulforhodamine B assay in immortalized cancer cell lines. Stimulator of interferon genes pathway activation was assessed by western blot analysis using human THP-1-derived macrophages. The production of pro-inflammatory cytokines from these macrophages was also evaluated via enzyme-linked immunosorbent assay. Key findings: Both compounds 1 and 3 displayed moderate inhibitory effects on the cancer cells, including a cisplatin-resistant cell line, with IC50 values in the range of 10–20 µM. All three xanthones activated the stimulator of interferon genes, as evidenced by phosphorylation of tank-binding kinase 1, the stimulator of interferon genes protein and interferon regulatory factor 3. Furthermore, treatment of these macrophages with compounds 1–3 led to the production of pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor α and interleukin 1β. Conclusions: In conclusion, the isolated xanthones, including the novel garcicowanone I, displayed promising anticancer and immunomodulatory activity that warrants further research.
- Subjects
GARCINIA; INTERFERON regulatory factors; ENZYME-linked immunosorbent assay; WESTERN immunoblotting; ANTINEOPLASTIC agents; BARK; VENOM
- Publication
Journal of Pharmacy & Pharmacology, 2023, Vol 75, Issue 8, p1058
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1093/jpp/rgad038