Phytomedicine
Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address:
Published: July 2023
Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-associated mortality worldwide. Myosin-9's role in HCC and the anti-HCC effect of the drugs targeting Myosin-9 remain poorly understood so far. Candidate antitumor agents obtained from natural products have attracted worldwide attention. Usenamine A is a novel product, which was first extracted in our laboratory from the lichen Usnea longissima. According to published reports, usenamine A exhibits good antitumor activity, while the mechanisms underlying its antitumor effects remain to be elucidated.
Purpose: The present study investigated the anti-hepatoma effect of usenamine A and the underlying molecular mechanisms, along with evaluating the therapeutic potential of targeting Myosin-9 in HCC.
Methods: The CCK-8, Hoechst staining, and FACS assays were conducted in the present study to investigate how usenamine A affected the growth and apoptosis of human hepatoma cells. Moreover, TEM, acridine orange staining, and immunofluorescence assay were performed to explore the induction of autophagy by usenamine A in human hepatoma cells. The usenamine A-mediated regulation of protein expression in human hepatoma cells was analyzed using immunoblotting. MS analysis, SPR assay, CETSA, and molecular modeling were performed to identify the direct target of usenamine A. Immunofluorescence assay and co-immunoprecipitation assay were conducted to determine whether usenamine A affected the interaction between Myosin-9 and the actin present in human hepatoma cells. In addition, the anti-hepatoma effect of usenamine A was investigated in vivo using a xenograft tumor model and the IHC analysis.
Results: The present study initially revealed that usenamine A could suppress the proliferation of HepG2 and SK-HEP-1 cells (hepatoma cell lines). Furthermore, usenamine A induced cell apoptosis via the activation of caspase-3. In addition, usenamine A enhanced autophagy. Moreover, usenamine A administration could dramatically suppress the carcinogenic ability of HepG2 cells, as evidenced by the nude mouse xenograft tumor model. Importantly, it was initially revealed that Myosin-9 was a direct target of usenamine A. Usenamine A could block cytoskeleton remodeling through the disruption of the interaction between Myosin-9 and actin. Myosin-9 participated in suppressing proliferation while inducing apoptosis and autophagy in response to treatment with usenamine A. In addition, Myosin-9 was revealed as a potential oncogene in HCC.
Conclusions: Usenamine A was initially revealed to suppress human hepatoma cells growth by interfering with the Myosin-9/actin-dependent cytoskeleton remodeling through the direct targeting of Myosin-9. Myosin-9 is, therefore, a promising candidate target for HCC treatment, while usenamine A may be utilized as a possible anti-HCC therapeutic, particularly in the treatment of HCC with aberrant Myosin-9.
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http://dx.doi.org/10.1016/j.phymed.2023.154895 | DOI Listing |
Cell Mol Biol (Noisy-le-grand)
January 2025
Université Joseph KI-ZERBO, Laboratoire de Biologie Moléculaire et de Génétique (LABIOGENE), 03 BP 7021 Ouagadougou 03, Burkina Faso.
Hepatitis B virus (HBV) is a significant cause of liver disease and cancer worldwide. Understanding the genetic factors influencing HBV evolution is crucial for developing effective prevention and treatment strategies. Host genetic and environmental factors particularly influence the evolution of this infection.
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January 2025
Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Berberine (BBR), an isoquinoline alkaloid abundant in Coptis chinensis, exhibits anti-tumor and hypoglycemic properties. The regulation of tumor cell homeostasis and metabolism is greatly influenced by Hypoxia-inducible factor-1α (HIF-1α). This research aims to elucidate whether BBR inhibits the progression of hepatocellular carcinoma (HCC) by modulating HIF-1α expression.
View Article and Find Full Text PDFPak J Pharm Sci
January 2025
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China/Province Multi-Component Chinese Medicine Engineering Technology Research Center of Liaoning, Dalian, China/Modern Traditional Chinese Medicine Research and Engineering Laboratory of Liaoning, Dalian, China.
Chebulagic acid and chebulinic acid are the two tannin compounds with the highest content in Terminalia chebula, they were separated by ODS column eluted with 20% methanol and 35% methanol, respectively. The compounds were identified by comparing the data of H NMR and C NMR with the literature; HPLC method was used to investigate the stable storage conditions of chebulagic acid and chebulinic acid; lipopolysaccharide (LPS) induced in vivo inflammation model and RAW264.7 macrophage in vitro inflammatory model to evaluate the anti-inflammatory activities of chebulagic acid and chebulinic acid.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
January 2025
Traditional Chinese Medicine Department of Guangxi Medical University Cancer Hospital, Nanning 530021, China. *Corresponding author, E-mail:
Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC.
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January 2025
Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, P. R. China.
Background: The insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in IGF2 and H19 overexpression regulation and its role in HCC.
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