INVESTIGATIONAL NEW DRUGS
·
2023
·Vol. 41
·期 1
·134-141
·
IF 3.4
Yan Gaobo,Zhang Hongyan,Li Yan,Miao Guoqiang,Liu Xiaolei,Lv Qifan
Lysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with IC 50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 μM, respectively. In comparison, it was a selective LSD1 inhibitor with an IC 50 value of 970.27 nM and could induce a significant accumulation of LSD1 substrates H3K9me1, H3K9me2, and H3K4me1 in a concentration-dependent manner in DU145 cells. According to docking studies, it formed hydrogen bonds with the Thr11, Lys14, and Arg8 residues of LSD1. Importantly, while it displayed potent antitumor efficacy in vivo, it did not show obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B, as a novel LSD1 inhibitor, is a potential candidate that can be used for the treatment of prostate cancer in clinics.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Ouwen Xu,Shuyu Wan,Yuheng Zhang,Jiawei Li,Xiashi Zhu
A dual-"on-off-on" fluorescent probe based on nitrogen-doped carbon quantum dots (BG-NCDs) with the dual-excitation property was developed, which had a blue emission peak at 398 nm and a green emission peak at 518nm when excited at 298nm and 404nm, respectively. BG-NCDs were characterized by TEM, XPS, and FT-IR. The results showed that (1) the Fe (III) and ascorbic acid (AA) could “turn off/turn on” the blue fluorescence of BG-NCDs, the blue fluorescence of BG-NCDs was used as an “on-off-on” fluorescent probe to detecting the Fe (III) and AA in the linear ranges of 0.04–20.00 mg/L and 0.57–10.00 mg/L, the LODs were as low as 0.012 mg/L and 0.19 mg/L; (2) the presence of Cu (II) and glutathione (GSH) could “turn off/turn on” the green fluorescence of BG-NCDs, the “on-off-on” process of green fluorescence of BG-NCDs could be established as a fluorescence probe to detecting Cu (II) and GSH in the linear ranges of 1.08–16.00 mg/L and 2.46–32.00 mg/L, with LODs of 0.36 mg/L and 0.86 mg/L. The method was applied to determination analytes in real samples with satisfactory results. BG-NCDs displayed low cytotoxicity and was multicolored imaging DU145 cells successfully.
研究领域:
材料科学
·
分析化学
·
生物化学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 2
·1795-1801
·
IF 1.261
Qiang Zhang,Guangdong Cheng,Hongbin Qiu,Yuexin Wang,Jingtao Wang,Hui Xu,Tao Zhang,Lixin Liu,Ye Tao,Zhongjuan Ren
Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer cases and may be a potential therapeutic target in the treatment of prostate cancer. The present study evaluated the cytotoxicity of three flavonoids (genistein, luteolin and quercetin) towards DU145 prostate cancer cells, and investigated the effect of these flavonoids on PSCA expression. The results demonstrated that genistein, luteolin and quercetin inhibited the growth of DU145 cells in a dose-dependent manner (P<0.05) and induced morphological changes characteristic of apoptosis in DU145 cells. Flow cytometry analysis also indicated that the flavonoids induced S phase cycle arrest in DU145 cells. Notably, it was observed that expression of PSCA was inhibited at the mRNA (P<0.05) and protein levels in DU145 cells following flavonoid treatment compared with the control. These results suggest that flavonoids may be potential therapeutic agents in the treatment and prevention of prostate cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-20
·
IF 11.4
Xu Wenjing,Li Yingqiu,Liu Lumei,Xie Jing,Hu Zongren,Kuang Shida,Fu Xinying,Li Bonan,Sun Tiansong,Zhu Congxu,He Qinghu,Sheng Wen
Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3 + CD8 + IFN-γ, CD3 + CD8 + Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.
研究领域:
肿瘤学
·
免疫学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）