RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most serious malignancies. The main features of HCC are vascular invasion and drug resistance. Ferroptosis is a novel cell program that is involved in several diseases, such as cancer. Heat shock protein beta 1 (HSPB1) is a major component of heat shock proteins. A recent study showed that HSPB1 could be a new therapeutic target for colorectal cancer with 5-fluorouracil-acquired resistance. However, the functional role of HSPB1 in HCC remains unclear. AIM: The aim of this study is to clarify HSPB1 expression in HCC and its potential therapeutic and prognostic value. METHODS: We collected data on HSPB1 expression levels in HCC and normal liver tissues from The Cancer Genome Atlas and Gene Expression Omnibus databases. We then validated it using immunohistochemistry (IHC). Receiver operating characteristic and Kaplan-Meier survival curves were used to investigate the role of HSPB1 in the prognosis analysis of HCC. Further, we used the online Search Tool for the Retrieval of Interacting Genes/Proteins website, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes to conduct enrichment analysis and identify the predictive signaling pathways. Meanwhile, we used the TIMER and GSVA package of R (v3.6.3) to analyze the association between HSPB1 and immunocyte infiltration. RESULTS: Compared to normal tissues, there was differential expression of HSPB1 in pan-cancers. HSPB1 expression was higher in HCC tissues than in normal tissues (p<0.05). There was an evident significant difference between HSPB1 mRNA levels and histologic grade, vascular invasion, and alpha-fetoprotein level (all p values<0.05). Univariate analysis indicated that HCC patients with high HSPB1 levels had shorter overall survival rates than those with low HSPB1 levels (p<0.05). MAPK14, HSPA8, MAPKAPK3, MAPKAPK5, and MAPKAPK2 are essential proteins that interact with HSPB1. There was a significant correlation between HSPB1 expression levels and immune cell infiltration, including CD4+ T cells (r=0.203, p<0.05). CONCLUSION: High HSPB1 expression is closely associated with a worse prognosis in HCC patients, and HSPB1 may be a target of immunotherapy in HCC.
RESUMO
A chemical investigation on the 80% EtOH extract of the aerial parts of Kopsia fruticosa led to five new indole alkaloids, kopsifolines G-K (1-5), and one known alkaloid, kopsifoline A (6). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated components were evaluated in vitro for cytotoxic activities against seven tumor cell lines, antimicrobial activities against two Gram-positive bacteria and five Gram-negative bacteria, and antifungal activities against five pathogens. As a result, alkaloids 3-5 exhibited some cytotoxicity against all of seven tested tumor cell lines (HS-1, HS-4, SCL-1, A431, BGC-823, MCF-7, and W480) with IC50 values of 11.8-13.8, 10.3-12.5, and 7.3-9.5⯵M, respectively. Alkaloids 3-5 also possessed significant antimicrobial and antifungal activities which was reported for the first time for the alkaloids isolated from Kopsia genus.