MOLECULES
·
2020
·Vol. 25
·期 23
·5778
·
IF 3.267
Yangke Wanyan,Xixi Xu,Kehang Liu,Huidan Zhang,Junai Zhen,Rong Zhang,Jumei Wen,Ping Liu,Yuqing Chen
Inhibition of the glycolytic pathway is a critical strategy in anticancer therapy because of the role of aerobic glycolysis in cancer cells. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) has shown potential in combination with other anticancer agents. Buforin IIb is an effective antimicrobial peptide (AMP) with broad-spectrum anticancer activity and selectivity. The efficacy of combination treatment with 2-DG and buforin IIb in prostate cancer remains unknown. Here, we tested the efficacy of buforin IIb as a mitochondria-targeting AMP in the androgen-independent human prostate cancer cell line DU145. Combining 2-DG with buforin IIb had a synergistic toxic effect on DU145 cells and mouse xenograft tumors. Combination treatment with 2-DG and buforin IIb caused stronger proliferation inhibition, greater G1 cell cycle arrest, and higher apoptosis than either treatment alone. Combination treatment dramatically decreased L-lactate production and intracellular ATP levels, indicating severe inhibition of glycolysis and ATP production. Flow cytometry and confocal laser scanning microscopy results indicate that 2-DG may increase buforin IIb uptake by DU145 cells, thereby increasing the mitochondria-targeting capacity of buforin IIb. This may partly explain the effect of combination treatment on enhancing buforin IIb-induced apoptosis. Consistently, 2-DG increased mitochondrial dysfunction and upregulated Bax/Bcl-2, promoting cytochrome c release to initiate procaspase 3 cleavage induced by buforin IIb. These results suggest that 2-DG sensitizes prostate cancer DU145 cells to buforin IIb. Moreover, combination treatment caused minimal hemolysis and cytotoxicity to normal WPMY-1 cells. Collectively, the current study demonstrates that dual targeting of glycolysis and mitochondria by 2-DG and buforin IIb may be an effective anticancer strategy for the treatment of some advanced prostate cancer.Keywords:buforin IIb;2-Deoxy-d-glucose;mitochondria;glycolysis;prostate cancer
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Shuyi Zhou,Xixi Hou,Ling Li,LiHao Guo,Huili Wang,Longfei Mao,Leilei Shi,Miaomiao Yuan
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, causing a huge number of deaths each year. Traditional chemotherapy for PCa mostly focused on targeting androgen receptors. However, some of the patients would develop resistance to hormonal therapy. In these cases, it is suggested for these patients to administer treatments in combination with other chemotherapeutics. Current chemotherapeutics for metastatic castration-resistant PCa could hardly reach satisfying effects, therefore it is crucial to explore novel agents with low cytotoxicity. Herein, a common drug against the human immunodeficiency virus (HIV), the dolutegravir (DTG) was modified to become a series of dolutegravir-1,2,3-triazole derivatives. Among these compounds, the 4d and 4q derivatives were verified with high anti-tumor efficiency, suppressing the proliferation of the prostate cancer cells PC3 and DU145. These compounds function by binding to the poly (adenosine diphosphate-ribose) polymerase (PARP), inactivating the PARP and inducing DNA damage in cancer cells. It is noteworthy that the 4d and 4q derivatives showed almost no impact on normal cells and mice. Thereby, the results reveal that these dolutegravir-1,2,3-triazole compounds are potential chemotherapeutics for PCa treatment.
研究领域:
肿瘤学
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药理学
·
化学生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2024
·
IF 2.1
Wang Rui,Liao Zhaoping,Liu Chunhua,Yu Shifang,Xiang Kaihua,Wu Ting,Feng Jie,Ding Senjuan,Yu Tingao,Cheng Gang,Li Sanlian
Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that Cellular Retinoic Acid Binding Protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility, and apoptosis in multiple cancers, yet the effect of CRABP2 on PCa is poorly reported. The CRABP2 expression in different PCa cell lines and its effect on different cellular functions were various. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Besides, CRABP2 had no influence on the cell cycle distribution of PCa cells. RNA-seq assay showed that overexpressing CRABP2 up-regulated Laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in PI3K/AKT and MAPK signaling pathway. The following WB experiments also confirmed the up-regulated LAMB3 protein level and the activation of PI3K/AKT and MAPK signaling pathways. Moreover, overexpressing CRABP2 inhibited tumor growth significantly in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signaling pathways through upregulating LAMB3 in PCa.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
✓ 已验证
DOI
高影响因子
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
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 34
·期 4
·817-824
·
IF 3.766
Mingming Zhu,Xi Yu,Zongmei Zheng,Jiaming Huang,Xuepan Yang,Hongfei Shi
Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3β and β-catenin, along with downregulation of Wnt/β-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/β-catenin pathway, we found activation of Wnt/β-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/β-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 3.7
Lingke Feng,Rong Pan,Ke Ning,Wen Sun,Yirong Chen,Yuanyuan Xie,Mingzhu Wang,Yan Li,Ling Yu
Cell motility is crucial in cancer metastasis, and understanding its regulation in tumor cells is vital for developing anti-metastatic therapies. Traditional 2D cell culture assays provide insights into cell migration but fail to replicate the complex 3D architecture of tissues in vivo . 3D cell culture models like tumor spheroids have been applied for cell migration tests. This study investigates the role of spheroid maturity in tumor cell motility, hypothesizing that spheroid maturity mirrors physiological conditions in solid tumors. Human prostate (DU145), breast (MCF-7), and murine breast (EMT-6) cancer cells were cultured into spheroids of varying ages (3, 7, and 11 days). The migration and invasion of these spheroids were analyzed, revealing that 11-day-old DU145 spheroids demonstrated the greatest horizontal migration, correlating with RNA-seq data showing increased cell adhesion, cytoskeleton dynamics, and motility pathways. Confocal microscopy and single-cell analysis indicated higher reactive oxygen species (ROS) levels in mature spheroids, potentially activating motility pathways. Additionally, DU 145 spheroids were treated with chemotherapy reagent Doxorubicin (DOX), and the results showed that spheroids culture for 7 and 11 days exhibited greater resistance to DOX compared to spheroids cultured for 3 days. These findings highlight the importance of considering spheroid maturity in cancer research and drug development, emphasizing the need for systematic analysis of spheroid growth conditions to ensure reproducible and reliable experimental settings.
研究领域:
癌症生物学
·
细胞生物学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Oncology Letters
·
2020
·Vol. 20
·期 4
·1-1
·
IF 2.311
Peng He,Guoguang Xiong,Wei Guo,Guanjun Jiang,Yun Li,Hao Li
Long non‑coding RNA colon cancer associated transcript 2 (CCAT2) is dysregulated in a number of different types of human cancer, and affects cancer progression via the Wnt/β‑catenin signaling pathway. However, the roles of CCAT2 and the Wnt/β‑catenin signaling pathway in prostate cancer (PCa) are not completely understood. The present study aimed to investigate the potential mechanism of CCAT2 in PCa. In the present study, the reverse transcription‑quantitative PCR (RT‑qPCR) results indicated that CCAT2 expression was significantly upregulated in PCa tissues, and DU145 and PC3 cell lines compared with normal prostate tissues and the epithelial RWPE‑1 cell line, respectively. Functional assays indicated that CCAT2 downregulation inhibited DU145 and PC3 cell proliferation, cell cycle, migration and invasion. In addition, the luciferase reporter assay, RT‑qPCR and western blotting results indicated that CCAT2 regulated transcription factor 7 like 2 (TCF7L2) expression by binding to microRNA‑217. Further western blotting and TOPFlash assays indicated that CCAT2‑knockdown inhibited the Wnt/β‑catenin signaling pathway in DU145 and PC3 cell lines by inhibiting the expression of TCF7L2. However, CCAT2‑knockdown‑mediated effects were reversed by the Wnt/β‑catenin signaling pathway activator lithium chloride (LiCl). Further cell experiments suggested that LiCl treatment reversed CCAT2‑knockdown‑mediated inhibition of PCa cell proliferation, cell cycle, epithelial‑mesenchymal transition, migration and invasion. Overall, the results indicated that CCAT2 regulated PCa via the Wnt/β‑catenin signaling pathway; therefore, CCAT2 may exhibit key role during the progression of PCa and may serve as a therapeutic target for the disease.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症遗传学
✓ 已验证
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 PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Baoyan Ding,Wei Meng,Xiaoling Zang,Zhihua Lv
A small molecule, (S)-ethyl 1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (SEC), has been reported to be capable of suppressing metastasis of prostate cancer (PCa) cells. In this study, SEC was used to study the metabolic responses of PCa cell lines (LNCaP, PC3, and DU145) with different metastatic potential and the alterations of mTOR, p-mTOR, AMPK, and p-AMPK levels, when the PCa cells were inhibited. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based analysis showed that SEC induced the decreases of intracellular metabolites including glutamic acid, glutamine, and histidine (LNCaP); creatinine, citric acid/isocitric acid, and aspartic acid (PC3); and spermidine, S-hydroxymethylglutathione, LPE (20:3), and palmitic amide (DU145), and the increases of intracellular LPC (18:0) (LNCaP); tyrosine, pyroglutamic acid/pyrroline hydroxycarboxylic acid (PC3); and tyrosine, phenylalanine, phenylacetylglycine, spermine, histidine, and choline (DU145). SEC also caused the decrease of extracellular N1-acetylspermidine (LNCaP), erythronic acid/threonic acid (PC3 and DU145), and nicotinic acid/picolinic acid (DU145), and the increase of extracellular 5’-methylthioadenosine (DU145). High metastatic PC3 and DU145 cells exhibited changes in aromatic amino acid metabolism including tyrosine metabolism, phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism (PC3 and DU145), TCA cycle (PC3), arginine and proline metabolism, and glycerophospholipid metabolism (DU145), different from the low metastatic LNCaP cells, which had changes in alanine, aspartate, and glutamate metabolism, and arginine biosynthesis. In addition, the levels of p-mTOR and p-AMPK were shown to be obviously downregulated and upregulated, respectively, in high metastatic PC3 and DU145 cells upon SEC inhibition, while this behavior was not detected in LNCaP cells.
研究领域:
肿瘤学
·
代谢组学
·
药理学
✓ 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）