Endometrial carcinoma is one of the most common types of cancer among women. The progression of cancer occurs via the Epithelial- Mesenchymal Transition (EMT) pathway. Cells lose their epithelial properties and become mobile. For this reason, the EMT process is one of the most important step to be targeted in cancer treatment. Oleandrin is a cardiac glycoside and its use is limited due to its narrow therapeutic index. In this study, we aimed to evaluate effects of lower level Oleandrin doses on EMT process in endometrial carcinoma. Oleandrin was administrated to Ishikawa endometrial adenocarcinoma cells at different doses and times. IC50 dose was determined by XTT proliferation test. Expression analysis of EMT-related genes was then performed by qRT-PCR. Invasion and colony formation abilities of cells were examined microscopically. Finally, the migration analysis of cancer cells was determined by the Wound Healing Assay. The IC50 dose of Oleandrin applied to Ishikawa cells was determined as 75.3 nM at the 48 h. According to qRT-PCR analysis, expression levels of ZEB1, FN1, ITGB1, VIM, SMAD2, SNAI1, SNAI2, SNAI3, and TGFB3 genes significantly decreased, but TIMP2, TIMP3, ITGAV and GSK3B genes significantly increased. In addition, Oleandrin significantly reduced colony formation and invasion of Ishikawa cells. According to the Wound Healing analysis, the migratory abilities of the Oleandrin-treated cells were reduced compared to the control. Low dose Oleandrin suppresses the EMT pathway in Ishikawa cells. It has been shown that Oleandrin significantly suppresses the cell's colony formation, invasion and migration ability both in gene expression analyzes and microscopically.
The most common cancer seen in men worldwide is prostate cancer. It ranks second in the deadliest cancer types. Viburnum opulus is a type of tree that produces small red fruits. Shell, fruit, flower and juice of V. opulus are widely used in various fields and traditional medicine. Studies have shown that V. opulus also has an anti-cancer effect. For this purpose, the apoptotic effect of V. opulus was investigated in the LNCaP prostate cancer cell line. LNCaP human prostate cancer cells were treated with V. opulus extract in a 1-200 µg/mL concentration range. IC50 dose of V. opulus extract was determined by cell viability test XTT. Expressions of genes related to apoptosis after extract application were determined by quantitative RT-PCR analysis. V. opulus showed the cytotoxic effect on the LNCaP cell line, and differences in the expressions of apoptosis-related genes were observed. Significant increases in BAX, CASP7, CASP8 and P53 expressions showed that the pro-apoptosis pathway was active, while CASP3 expression was significantly decreased. The extrinsic apoptosis pathway of might be effective due to increased CASP7 and CASP8 gene expression. However, the molecular mechanism of apoptotic activity of V. opulus needs to be investigated in more detail.
2 June 2025 in Central European Journal of Immunology
Introduction: Macrophages are the primary cells of the mononuclear system. Studies have demonstrated that macrophages play an active role in the pathophysiology of cancers due to their remarkable adaptation capacities. The objective of this investigation was to examine the impact of apelin on macrophage polarization in the colon cancer microenvironment. Material and methods: In this study, the colon adenocarcinoma cell line SW480 and mouse macro- phage cells RAW264.7 were used. Using shRNA, expression of the apelin gene was suppressed in SW480 cells. RAW264.7 cells were co-cultured with SW480 cells with the apelin gene silenced and no shRNA introduced. qRT-PCR and protein expression analysis were applied to assess the effect of apelin on inflammation-related genes and proteins, respectively, in co-cultured RAW264.7 cells. Results: In comparison to the control, apelin knockdown led to significantly lower apelin expression in SW480 cells and a significant greater pro-inflammatory response in co-cultured macrophages. The ex- pression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1 genes were significantly elevated, while the amount of IL-10, which is known as an anti-inflammatory cytokine, was dramatically decreased. Pro-inflammatory genes, namely IL-1, IL-2 and TNF-α, were found to be downregulated, and anti-inflammatory genes, including IL-10 and transforming growth factor b (TGF-β), were found to be upregulated in the apelin-knockdown group compared to the control. Remarkably, the expression levels of IL-1, IL-6, and TNF-α proteins, which are involved in macrophage polarization, were in agreement with the qRT-PCR data. Conclusions: These results indicate that the apelin peptide may be associated with the dense presence of M2-type macrophages in the cancer microenvironment, suggesting it as a therapeutic target for cancer cells.