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- Title
Marinobazzanan, a Bazzanane-Type Sesquiterpenoid, Suppresses the Cell Motility and Tumorigenesis in Cancer Cells.
- Authors
Pulat, Sultan; Hillman, Prima F.; Kim, Sojeong; Asolkar, Ratnakar N.; Kim, Haerin; Zhou, Rui; Taş, İsa; Gamage, Chathurika D. B.; Varlı, Mücahit; Park, So-Yeon; Park, Sung Chul; Yang, Inho; Shin, Jongheon; Oh, Dong-Chan; Kim, Hangun; Nam, Sang-Jip; Fenical, William
- Abstract
Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of 1 were determined by the modified Mosher's method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6R, 7R, 9R, and 10R. It was found that compound 1 was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 μM. However, compound 1 was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 μM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound 1 suppressed β-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, 1 also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.
- Subjects
CANCER cell motility; VIBRATIONAL circular dichroism; WNT signal transduction; NOTCH signaling pathway; CANCER cell migration; CANCER cells; STOMACH cancer; NOTCH genes
- Publication
Marine Drugs, 2023, Vol 21, Issue 3, p153
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md21030153