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Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo , accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N -acetyl- l -cysteine, l -glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[ O -methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment. Baicalin exerts its anticancer activity in bladder cancer by inducing ferritin heavy chain 1 (FTH1)-dependent ferroptosis, which will hopefully provide great therapeutic potential for bladder cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Dysregulation of the long intergenic noncoding RNA 01315 (LINC01315) has recently been demonstrated in cancer. However, the role of LINC01315 in papillary thyroid cancer (PTC) has not been determined. We attempted to determine the function of LINC01315 in PTC. The levels of LINC01315 were higher in thyroid carcinoma tissues and cell lines compared with that in noncancerous tissues or normal cells, respectively. LINC01315 knockdown significantly inhibited the in vitro colony formation and invasion of PTC cells. Upregulation of LINC01315 produced opposite effects. Bioinformatic analysis and luciferase reporter assays indicated direct binding of miR‐497‐5p to LINC01315. Gain‐ and loss‐of‐function assays indicated that miR‐497‐5p acts as a suppressive miRNA in PTC. Furthermore, LINC01315 facilitated the growth and invasion of PTC cells by sponging miR‐497‐5p. Our results demonstrated the critical role of the LINC01315‐miR‐497‐5p axis in the growth and invasion of PTC cells. [ABSTRACT FROM AUTHOR]

Background: Our study investigated the expression levels of miR-1231 in prostate cancer tissues and cell lines and explored its potential prognostic significance as well as its functional effects on prostate cancer cells. Methods: miR-1231 expression levels were detected in prostate cancer tissues and prostate cancer cell lines using qRT-PCR. The prognostic significance of miR-1231 in prostate cancer was assessed using the Kaplan-Meier curve and Cox regression analyses. Evaluation of the impact of ectopic expression or inhibition of miR-1231 on aggressive tumor behavior (cellular proliferation, migration, and invasion) of prostate cancer cell lines involved the CCK-8 and Transwell assays. Results: miR-1231 expression was downregulated in both prostate cancer tissues and cell lines. Downregulation of miR-1231 was significantly associated with lymph node metastasis, higher TNM stage, higher clinical stage, and shorter overall survival. The expression of miR-1231 was predicted as a prognostic factor for prostate cancer patients. Additionally, we found overexpression of miR-1231 suppressed proliferation, migration, and invasion of prostate cancer cell linesin vitro. EGFR was a direct target of miR-1231. Conclusion: Taken together, our results indicate that miR-1231 expression plays a tumor-suppressive role in prostate cancer. It is downregulated in prostate cancer and may suppress prostate cancer cell proliferation, migration, and invasion by targeting EGFR, and it may be a prognostic biomarker and potential therapeutic strategy for prostate cancer treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Juglone is a natural pigment, which has a cytotoxic effect against tumor cells. However, its cytotoxicity to human breast cancer cells (Michigan Cancer Foundation-7 [MCF7]) has not been demonstrated. Objective: The objective was to observe the effect of Juglone on the protein expression of caspase-3, 9 in the apoptosis of Human Breast Cancer Cells (MCF7) and apoptosis-related protein, Bcl-2-associated X protein (Bax), and B-cell lymphoma-2 (Bcl-2) and investigate in the inhibitory effect of MCF7. Materials and Methods: Methyl thiazolyl tetrazolium experiment was performed for the detection of the cell growth inhibition effect of MCF7. The apoptosis rate was detected by flow cytometry. Western Blot was used to detect the protein expression of Bax, Bcl-2, and caspase. The messenger RNA (mRNA) was tested using quantitative real-time polymerase chain reaction. Results: Juglone inhibited the growth of MCF7 cells in a concentration- and time-dependent manner and promotes the apoptosis of MCF7 cells in a concentration-dependent manner. Compared with control group, the Juglone group raised the expression of Bax protein (*P < 0.05), and the protein expression of Bcl-2 was decreased (*P < 0.05). The expression of caspase-3 protein was not changed, and the caspase-9 was significantly elevated in the high concentration of Juglone. Cleaved caspase-3, -9 protein was significantly raised (*P < 0.05). The mRNA levels of Bax, caspase-3, and caspase-9 in MCF7 cells of Juglone group were significantly increased compared with control, while the expression of Bcl-2 was suppressed obviously. Conclusion: Juglone inhibited the growth of MCF7 cells and promotes the apoptosis of MCF7 cells. Its mechanism in promoting MCF7 cell apoptosis may be related to the decrease of the expression of the mitochondrial pathway-associated apoptosis factor Bcl-2, increase of the protein expression of Bax, and mitochondrial pathway downstream caspase-3, 9. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of follicular thyroid carcinoma (FTC) and follicular adenoma (FA) before surgery is a clinical challenge. Many efforts have been made but most focusing on tumor cells, while the roles of tumor associated macrophages (TAMs) remained unclear in FTC. Here we analyzed the differences between TAMs in FTC and those in FA.Methods: We first analyzed the density of TAMs by CD68 immunostaining in 59 histologically confirmed FTCs and 47 FAs. Cytokines produced by FTC and FA were profiled using antibody array, and validated by quantitative PCR. Chemotaxis of monocyte THP-1 was induced by condition medium of FTC cell lines (FTC133 and WRO82-1) with and without anti-CCL15 neutralizing antibody. Finally, we analyzed CCL15 protein level in FTC and FA by immunohistochemistry.Results: The average density of CD68(+) cells was 9.5 ± 5.4/field in FTC, significantly higher than that in FA (4.9 ± 3.4/field, p < 0.001). Subsequently profiling showed that CCL15 was the most abundant chemokine in FTC compared with FA. CCL15 mRNA in FTC was 51.4-folds of that in FA. CM of FTC cell lines induced THP-1 cell chemotaxis by 33 ~ 77%, and anti-CCL15 neutralizing antibody reduced THP-1 cell migration in a dose-dependent manner. Moreover, we observed positive CCL15 immunostaining in 67.8% of FTCs compared with 23.4% of FAs.Conclusion: Our study suggested FTC might induce TAMs infiltration by producing CCL15. Measurement of TAMs and CCL15 in follicular thyroid lesions may be applied clinically to differentiate FTC from FA pre-operation. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) play a vital role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. The mechanisms that maintain the stemness of these cells remain largely unknown. Our previous study indicated that MALAT-1 may serve as an oncogenic long noncoding RNA in pancreatic cancer by promoting epithelial-mesenchymal transition (EMT) and regulating CSCs markers expression. More significantly, there is emerging evidence that the EMT process may give rise to CSCs, or at least cells with stem cell-like properties. Therefore, we hypothesized that MALAT-1 might enhance stem cell-like phenotypes in pancreatic cancer cells. In this study, our data showed that MALAT-1 could increase the proportion of pancreatic CSCs, maintain self-renewing capacity, decrease the chemosensitivity to anticancer drugs, and accelerate tumor angiogenesis in vitro. In addition, subcutaneous nude mouse xenografts revealed that MALAT-1 could promote tumorigenicity of pancreatic cancer cells in vivo. The underlying mechanisms may involve in increased expression of self-renewal related factors Sox2. Collectively, we for the first time found the potential effects of MALAT-1 on the stem cell-like phenotypes in pancreatic cancer cells, suggesting a novel role of MALAT-1 in tumor stemness, which remains to be fully elucidated. [ABSTRACT FROM AUTHOR]

Abstract The insect Blaps japanensis have been used as an ethnomedicine in China for the treatment of several disorders such as cancer and inflammation. Our investigation with this insect led to the isolation of eight new and two known phenolic compounds. The structures of the new compounds, blapsins C−J (1 – 8), were identified by spectroscopic data. The inhibitory activities of all the compounds except of 9 against human cancer cells (A549, K562 and Huh-7), COX-2, ROCK1, and JAK3 were evaluated. Several compounds were found to be biologically active in these assays. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract: A novel class of aromatic diacylhydrazine derivatives was designed as PLK1 inhibitors. All the 19 new synthesized compounds were assayed for antitumor activity against the respective cervical cancer cells. In which, nine compounds with better antitumor activities were further tested for their PLK1 inhibitory activity. Last, we have successfully found that compound 7k showed both the promising antitumor activity with IC50 of 0.17 μM against the cervical cancer cells, and also processed the most potent PLK1 inhibitory activity with IC50 of 0.03 μM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and PKL1 (PDB code: 1umw) protein. [Copyright &y& Elsevier]