Antiproliferative activities of auraptenol against drug-resistant human prostate carcinoma cells are mediated via programmed cell death, endogenous ROS production, and targeting the JNK/p38 MAPK signal pathways.

The Editors of JBUON issue an Expression of Concern to 'Antiproliferative activities of auraptenol against drugresistant human prostate carcinoma cells are mediated via programmed cell death, endogenous ROS production, and targeting the JNK/p38 MAPK signal pathways', by Yunli Liu, Xuedong Li, Zhaoyan Chen, Yunhui Chan; JBUON 2020;25(1):454-459; PMID: 32277668. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Antiproliferative activities of auraptenol against drug-resistant human prostate carcinoma cells are mediated via programmed cell death, endogenous ROS production, and targeting the JNK/p38 MAPK signal pathways.

PURPOSE: Prostate cancer is considered to be one of the most common cancers in men and as such there is a pressing need for finding new therapeutic agents to treat this disease. Therefore, the main purpose of the current research work was to study the anticancer effects of a naturally occurring coumarin- Auraptenol- against drug-resistant human prostate cancer cells and evaluate its effects on programmed cell death, reactive oxygen species (ROS) production, and JNK/p38 MAPK signalling pathway. METHODS: Cell proliferation was examined by CCK8 cell viability assay. Apoptosis-related studies were checked by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) and Hoechst staining, as well as flow cytometry using annexin V/propidium iodide (PI) assay. Western blot was used to study the effects of Auraptenol on apoptosis-related protein expressions including Bax, Bcl-2, as well as JNK/p38 MAPK signalling pathway. ROS production was evaluated by flow cytometry. RESULTS: The results showed that Auraptenol caused significant reduction in the viability of the human LNCaP prostate carcinoma cells in a dose-dependent manner, exhibiting an IC50 of 25 µM in cancer cells and IC50 of 100 µM in normal PNT2 cells. The AO/EB staining assay showed that Auraptenol inhibited the viability of cancer cells via induction of apoptotic cell death, which was associated with increase in Bax and decrease in Bcl-2 levels. Hoechst staining results also confirmed that Auraptenol induced programmed cell death. The apoptotic cells increased from 0.8% in the control to 32.5% in the study group at 50 µM concentration of Auraptenol. Auraptenol also induced an increase in ROS production in a dose-dependent manner. Finally, this molecule blocked the JNK/p38 MAPK signal pathway concentration-dependently in human prostate cancer cells. CONCLUSION: In conclusion, the current study indicates that this molecule could be developed as a potential anticancer drug against human prostate carcinoma provided further studies are carried out.

Inhibition of MicroRNA-381 Promotes Tumor Cell Growth and Chemoresistance in Clear-Cell Renal Cell Carcinoma.

BACKGROUND MicroRNA-381 (miR-381) is proven to be involved in many human tumors. Bioinformatics prediction suggests that miR-381 is decreased in renal cell carcinoma. However, its biological functions in clear-cell renal cell carcinoma (ccRCC) remain largely unknown. The present research aimed to evaluate miR-381 expression in renal cancer tissues and its effects on cell proliferation, growth, migration, and chemoresistance. MATERIAL AND METHODS Sixty pairs of ccRCC and the adjacent non-tumor specimens were collected during routine therapeutic surgery. Quantitative real-time PCR (qRT-PCR) assay was employed to examine miR-381 expression in the ccRCC tissues and the associated adjacent tissues (the normal tissues adjacent to tumor tissues). Cell transfection assay and Thiazolyl Blue Tetrazolium Bromide (MTT) assay were utilized to observe effects of miR-381 on the cell proliferation, growth, invasion, and chemoresistance in the Caki-1 cell line and 786-O cell line. Flow cytometry was used to assess cell apoptosis. Caki-1 cell and 786-O cell Xenograft BALB/c mouse models were established. RESULTS miR-381 expression was downregulated in ccRCC tissues in vivo and in cell lines in vitro. Downregulation of miR-381 promoted growth of cells and restrained the ccRCC cell apoptosis. Increased miR-381 combined with Ci and Pa suppressed the proliferation and enhanced the anti-tumor effects of Ci and Pa at tolerated concentrations in vitro. miR-381 inhibition promoted chemoresistance in vitro. CONCLUSIONS miR-381 levels were significantly downregulated in renal cancer tissues and miR-381 inhibition promoted tumor cell growth, migration, and chemoresistance.

Comprehensive characterization of immune- and inflammation-associated biomarkers based on multi-omics integration in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer in adults, and it is responsible for approximately 90-95% of cases. Although extensive evidence has suggested that many immune- and inflammation-related genes could serve as effective biomarkers in KIRC, the potential associations among immune-, inflammation- and KIRC-related genes has not been sufficiently understood. METHODS: Here, we integrated multiple levels of data to construct an immune-, inflammation- or KIRC-directed neighbour network (IIKDN network) and a KIRC-related gene-directed network (KIRCD network). RESULTS: Our analysis suggested that immune- and inflammation-related genes in the network have special topological characteristics and expression patterns related to KIRC. We further identified five core clusters that showed a tighter network structure and stronger correlation of expression from the KIRCD network. Specifically, multiple-level molecular characteristics were systematically portrayed, including somatic mutation, copy-number variant and DNA methylation for the genes in five core clusters. We discovered that the genes showed strong correlation with respect to the expression and methylation levels in these five core clusters. These five core clusters could become special prognostic biomarkers for KIRC, and functional analysis showed that they were associated with activation of the immune and inflammation systems and cancer progression. CONCLUSIONS: Our findings highlighted the novel role of the immune and inflammation genes in KIRC.

[Effects of 40H-tamoxifen on the proliferation and apoptosis of prostate stromal cells].

OBJECTIVE: To investigate the effects of 4OH-Tamoxifen (OHT) on proliferation and apoptosis of primary cultured prostate stromal cells. METHODS: Primarily cultured prostate stromal cells in vitro were treated with various concentrations (10(-8) mol/L - 10(-5) mol/L) of estradiol (E2), diethylstilbestrol (DES), OHT and the mixture of E2 (10(-8) mol/L - 10(-6) mol/L) with OHT (10(-7) mol/L) and then MTT and TUNEL were used to detect their proliferation and apoptosis respectively. RESULTS: There was a significant difference (P < 0.05) between OHT and estrogens in the effects on the apoptosis and proliferation of the primarily cultured prostate stromal cells. OHT suppressed proliferation of the prostate stromal cells at the concentrations from 10(-7) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = -0.383, P = 0.005); OHT (10(-7) mol/L) suppressed the proliferation stimulation effect of E2 at the concentrations from 10(-8) mol/L to 10(-6) mol/L (P < 0.05). OHT induced apoptosis at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = 0.349, P = 0.012). The apoptosis induced by OHT could not be reversed by E2 at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P > 0.05). CONCLUSION: OHT can obviously suppressed the proliferation and promote the apoptosis of primarily cultured prostate stromal cells, which might not be totally attributed to the competitive inhibition of the estrogen receptor.