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Introduction: Malignant melanoma (MM) is a highly aggressive skin tumour. Aim: To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene. Material and methods: Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay. Results: The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1β (IL-1β) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM. Conclusions: Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies. [ABSTRACT FROM AUTHOR]

【Objective】This work aims to investigate the effects and mechanisms of crude extract of F. suspensa leaves tea and its main components, phillyrin and Forsythia glycoside A, on the proliferation and migration function of hepatocellular carcinoma LM3.【Method】 Water extraction method was used to extract green tea and black tea from Forsythia suspensa leaves tea, HPLC was used to detect the content of effective components such as phillyrin and Forsythia glycoside A in F. suspensa green tea and F. suspensa black tea. CCK8 experiment was used to explore the effects of crude extracts of two types of F. suspensa leaves tea, phillyrin and Forsythia glycoside A on the proliferation of hepatocellular carcinoma LM3. Two crude extracts of Forsythia suspensa leaves tea, phillyrin and Forsythia glycoside A, were used to culture hepatocellular carcinoma LM3. The migration of cells was observed at 24, 48, 72, and 96 h, and the effects of the two crude extracts of F. suspensa leaves tea, phillyrin and Forsythia glycoside A on the migration of hepatocellular carcinoma LM3 were detected through the cell scratch test. To reveal the molecular mechanism of crude extract of F. suspensa leaves tea and its main components phillyrin and Forsythia glycoside A affect the proliferation and migration of hepatocellular carcinoma. The expressions of proliferation and migration-related gene Ki-67, Erk, PI3K and mTOR were detected using RT-PCR technology.【Result】Both the green tea and black tea extracts of F. suspensa leaves tea, as well as phillyrin and Forsythia glycoside A, significantly inhibited the proliferation and migration of hepatocellular carcinoma LM3, while Forsythia glycoside A significantly inhibited the migration of hepatocellular carcinoma line LM3. Among them, the crude extract of F. suspensa green tea significantly inhibited the proliferation and migration of HCC at low, medium, and high concentrations when 24, 48, and 72 h. The inhibitory effect of the crude extract of F. suspensa black tea on the proliferation and migration of LM3 cells continued to increase with increasing concentration, and the best inhibitory effect was achieved at high concentration for 72 h. The analysis of RT-PCR results suggests that its main mechanism of action may be achieved by reducing the expression levels of proliferation and migration related genes such as Ki-67.【Conclusion】 In summary, the crude extracts of F. suspensa green tea and F. suspensa black tea, as well as phillyrin and Forsythia glycoside A, can inhibit the proliferation or migration of HCC LM3 by reducing the expression of Ki-67. [ABSTRACT FROM AUTHOR]

Podostroma cornu-damae, one of the lethal toxic mushrooms, is known to contain macrocyclic trichothecene mycotoxins exhibiting potent cytotoxic effects, attracting attention as an important research subject for scientists interested in natural product chemistry and toxicity research. To investigate the mycotoxins from the toxic mushroom P. cornu-damae and evaluate their cytotoxic activities, the fungus was large-cultured on solid plates and successively extracted to acquire a crude methanol (MeOH) extract. After performing successive separation and purification processes, a total of eight macrocyclic trichothecenes were isolated from the MeOH extract of plate cultures of P. cornu-damae using the liquid chromatography/mass spectrometry (LC/MS)-guided isolation technique. Extensive interpretation of nuclear magnetic resonance (NMR) spectroscopic and high-resolution (HR)-electrospray ionization (ESI)-MS data allowed for the structural identification of all isolated macrocyclic trichothecenes, including satratoxin I (1), satratoxin H (2), roridin E (3), miophytocen D (4), roridin L-2 (5), trichoverritone (6), 12′-episatratoxin H (7), and roridin F (8). We conducted a cytotoxicity evaluation of compounds 1–8 against 4T1 breast cancer cells and fibroblast cell lines (L929 cells) using the Counting Kit-8 (CCK-8) cell viability assay to validate their cytotoxic potential. Our results indicated that compounds 1–6 lack anti-cancer effects on 4T1 cells and have minimal impact on the viability of the fibroblast cell line, L929 cells. In contrast, compounds 7 and 8 exhibited no cytotoxicity in normal cells (L929) and demonstrated specific cytotoxicity in breast cancer cell lines. Notably, the cytotoxic effects of compounds 7 and 8 in 4T1 cells were significantly stronger than those observed with free doxorubicin. These findings suggest that compounds 7 and 8 may possess targeted anti-cancer effects, specifically against breast cancer cells, emphasizing their efficient and selective toxicity towards breast cancer cells. [ABSTRACT FROM AUTHOR]

In the current study, a series of 1,3,4-oxadiazole and 1,2,4-triazole derivatives linked to quinazolinone were designed and synthesized by using Phase Transfer Catalysis. The structures of the synthesized compounds were confirmed by their IR, 1H NMR, 13C NMR, and HR-ESI-MS spectroscopic data, and their in vitro antiproliferative activities against A549, Hela, MCF-7 as well as L929 were detected by using CCK-8 assay. The results demonstrated that most of the compounds showed better growth inhibitory effect than 5-FU on A549, Hela, and MCF-7 cell lines. Especially, 2-(5-((3-bromophenyl)thio)-1,3,4-oxadiazole-2-yl)quinazolin-4(3H)-one (8o), 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) and 2-(4-amino-5-(o-tolylthio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9b) showed good antiproliferative activity against A549 cells with IC50 value of 3.46, 2.96, and 3.44 μM, respectively. 2-(4-Amino-5-((3,5-difluorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9h) and 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) had obvious inhibitory effects on Hela cells with IC50 values of 1.76 and 3.91 μM, respectively. 2-(4-Amino-5-((2-chlorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9i) showed high inhibitory activity against MCF-7 cells with IC50 value of 2.72 μM. Meanwhile, all compounds showed lower cytotoxicity to L929 cells than positive control drug 5-FU. In development, according to the above preliminary observation, these novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties could become potential molecular templates for searching new antitumor agents. [ABSTRACT FROM AUTHOR]

Podostroma cornu-damae, one of the lethal toxic mushrooms, is known to contain macrocyclic trichothecene mycotoxins exhibiting potent cytotoxic effects, attracting attention as an important research subject for scientists interested in natural product chemistry and toxicity research. To investigate the mycotoxins from the toxic mushroom P. cornu-damae and evaluate their cytotoxic activities, the fungus was large-cultured on solid plates and successively extracted to acquire a crude methanol (MeOH) extract. After performing successive separation and purification processes, a total of eight macrocyclic trichothecenes were isolated from the MeOH extract of plate cultures of P. cornu-damae using the liquid chromatography/mass spectrometry (LC/MS)-guided isolation technique. Extensive interpretation of nuclear magnetic resonance (NMR) spectroscopic and high-resolution (HR)-electrospray ionization (ESI)-MS data allowed for the structural identification of all isolated macrocyclic trichothecenes, including satratoxin I (1), satratoxin H (2), roridin E (3), miophytocen D (4), roridin L-2 (5), trichoverritone (6), 12′-episatratoxin H (7), and roridin F (8). We conducted a cytotoxicity evaluation of compounds 1–8 against 4T1 breast cancer cells and fibroblast cell lines (L929 cells) using the Counting Kit-8 (CCK-8) cell viability assay to validate their cytotoxic potential. Our results indicated that compounds 1–6 lack anti-cancer effects on 4T1 cells and have minimal impact on the viability of the fibroblast cell line, L929 cells. In contrast, compounds 7 and 8 exhibited no cytotoxicity in normal cells (L929) and demonstrated specific cytotoxicity in breast cancer cell lines. Notably, the cytotoxic effects of compounds 7 and 8 in 4T1 cells were significantly stronger than those observed with free doxorubicin. These findings suggest that compounds 7 and 8 may possess targeted anti-cancer effects, specifically against breast cancer cells, emphasizing their efficient and selective toxicity towards breast cancer cells.

Introduction: Malignant melanoma (MM) is a highly aggressive skin tumour., Aim: To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene., Material and Methods: Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay., Results: The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1β (IL-1β) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM., Conclusions: Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia Sp. z o. o.)

Background: It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer., Methods: The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion., Results: 40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group ( P < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened., Conclusions: Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.