scholarly journals Scutellaria Barbata D.Don (SBD) Extracts Suppressed Tumor Growth, Metastasis and Angiogenesis in Prostate Cancer Via PI3K/Akt Pathway

2021 ◽  
Author(s):  
Dongya Sheng ◽  
Bei Zhao ◽  
Wenjing Zhu ◽  
Tiantian Wang ◽  
yu peng
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Signalling Pathway ◽  
Growth Effect ◽  
Dependent Manner ◽  
Scutellaria Barbata ◽  
Mouse Xenograft Model

Abstract Background: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate that has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer.Materials and methods: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were performed to detected the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs.Results: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBE also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we performed that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBE. In addition, to its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells inhibited HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBE in vivo showed a significant decrease in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBE significantly inhibited the cell proliferation and promoted the damage of tumour tissues.Conclusions: Collectively, our in vitro and in vivo findings suggest that SBE had the potential to develop into a safe and potent alternative therapy for PCa patients.

scholarly journals FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
Maomao Guo ◽  
Weiwan Wang ◽  
Weican Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

scholarly journals FOXM1  modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
Maomao Guo ◽  
Weiwan Wang ◽  
Weican Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using the ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

scholarly journals FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
Maomao Guo ◽  
Weiwan Wang ◽  
Weican Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

scholarly journals FOXM1  modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
weiwan wang ◽  
Weican Zhang ◽  
zhibin xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background：Resistance to docetaxel is an important factor which affects the prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), participating in cell cycle progress and cell proliferation, has been reported to affect the sensitivity of chemotherapy. The present study aims to explore the role of FOXM1 in docetaxel resistance of PCa and how FOXM1 is associated with kinesin family member 20 A (KIF20A), which has been demonstrated to promote the development of therapeutic resistance in some cancers. Methods: We monitored cell growth by MTT and colony formation assays , and cell apoptosis and cell cycle through flow cytometry. Wound-healing and transwell assays were performed to detect cell migration and invasion. The mRNA and protein expression of gene were analyzed by by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. We determined the binding of FOXM1 on the KIF20A promoter by the ChIP assay. Tumorigenicity in nude mice was employed to assess tumorigenicity in vivo. Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, and suppressed cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). The opposite trend was found in their parental cells with exogenous FOXM1 overexpression. Furthermore, thiostrepton, a specific inhibitor for FOXM1, significantly attenuated docetaxel resistance in vitro and in vivo. Additionally, we found that FOXM1 and KIF20A were consistently overexpressed and highly correlated in PCa cells and tissues. Further studies demonstrated that FOXM1 regulated the expression of KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Moreover, KIF20A overexpression could partially reverse the effects of FOXM1 depletion on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP). Conclusions: our findings suggest that highly expressed FOXM1 may promote docetaxel resistance partly through the induction of KIF20A expression and provide insights into novel chemotherapeutic strategies for docetaxel resistance in PCa.

scholarly journals FOXM1  modulates docetaxel resistance in prostate cancer by regulating KIF20A

2020 ◽  
Author(s):  
Hongbo Yu ◽  
Zheng Xu ◽  
weiwan wang ◽  
zhibin xu ◽  
gangyi zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Docetaxel Resistance ◽  
Apoptosis Protein

Abstract Background：Resistance to docetaxel is an important factor which affects the prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), participating in cell cycle progress and cell proliferation, has been reported to affect the sensitivity of chemotherapy. The present study aims to explore the role of FOXM1 in docetaxel resistance of PCa and how FOXM1 is associated with kinesin family member 20 A (KIF20A), which has been demonstrated to promote the development of therapeutic resistance in some cancers.Methods: We monitored cell growth by MTT and colony formation assays and cell apoptosis and cell cycle through flow cytometry. Wound-healing and transwell assays were performed to detect cell migration and invasion. Gene expression was analyzedby quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. We determined the binding of FOXM1 on the KIF20A promoter by the ChIP assay. Tumorigenicity in nude mice was employed to assess tumorigenicity in vivo.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest while hampered cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). The opposite trend was found in their parental cells with exogenous FOXM1 overexpression. Furthermore, thiostrepton, a specific inhibitor for FOXM1, significantly attenuated docetaxel resistance in vitro and in vivo. Additionally, we found that FOXM1 and KIF20A were consistently overexpressed and highly correlated in PCa cells and tissues. Further studies demonstrated that FOXM1 regulated the expression of KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Moreover, KIF20A overexpression could partially reverse the effects of FOXM1 depletion on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (Bcl-2 and PARP).Conclusions: our findings suggest that FOXM1 may promote docetaxel resistance partly through the induction of KIF20A expression and provide insights into novel chemotherapeutic strategies for docetaxel resistance in PCa.

Effect of Metformin Intervention on Pancreatic β-Cell Apoptosis

2022 ◽  
Vol 12 (4) ◽  
pp. 873-877
Author(s):  
Dongqian Xie ◽  
Zhicheng Gao ◽  
Mei Liu ◽  
Defeng Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
High Glucose Condition ◽  
M Phase ◽  
Signaling Activation

Metformin is shown to have hypoglycemic effects. However, the relationship between metformin’s intervention in FFA-induced endoplasmic reticulum stress-mediated insulin resistance (IR) and insulin β-cell apoptosis under high-glucose condition remains unclear. Our study intends to assess their relationship. Human pancreatic β-cells were treated with metformin and cell proliferation and IR were detected by MTT assay along with detection of Wnt/β-catenin signaling by RT-PCR, cell cycle and apoptosis by flow cytometry. Metformin inhibited β cell proliferation which was mediated by FFA-induced endoplasmic reticulum stress in a time-dependent and dose-dependent manner as well as induced cell cycle arrest at G2/M phase. In addition, metformin inhibited β-catenin signaling activation and decreased the expression of c-myc, Dvl-2, survivin, Dvl-3, GSK-3β (p-ser9) and promoted GSK-3 (p-tyr216) and Axin-2 expression. In conclusion, metformin inhibits Wnt/β-catenin signaling and promotes FFA to induce endoplasmic reticulum stress, thereby mediating pancreatic β-cells behaviors.

Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (11/12) ◽  
pp. 997-1007 ◽  
Author(s):  
Katerina Gioti ◽  
Anastasia Papachristodoulou ◽  
Dimitra Benaki ◽  
Sophia Havaki ◽  
Apostolos Beloukas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Silybum Marianum ◽  
Altered Expression ◽  
Expression Levels ◽  
Branched Chain

AbstractSilymarin-enriched extract (SEE) is obtained from Silybum marianum (Asteraceae). Doxorubicin (DXR) is a widely used chemotherapeutical yet with severe side effects. The goal of the present study was to assess the pharmacologic effect of SEE and its bioactive components silibinin and silychristine when administrated alone or in combination with DXR in the human prostate cancer cells (PC-3). PC-3 cells were treated with SEE, silibinin (silybins A and B), silychristine, alone, and in combination with DXR, and cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis, and autophagy rate were assessed by flow cytometry. Expression levels of autophagy-related genes were quantified by qRT-PCR, ELISA and western blot while transmission electron microscopy was performed to reveal autophagic structures. Finally, NMR spectrometry was used to identify specific metabolites related to autophagy. SEE inhibited PC-3 cell proliferation in a dose-dependent manner while the co-treatment (DXR-SEE) revealed an additive cytotoxic effect. Cell cycle, apoptosis, and autophagy variations were observed in addition to altered expression levels of autophagy related genes (LC3, p62, NBR1, Beclin1, ULK1, AMBRA1), while several modifications in autophagic structures were identified after DXR-SEE co-treatment. Furthermore, treated cells showed a different metabolic profile, with significant alterations in autophagy-related metabolites such as branched-chain amino acids. In conclusion, the DXR-SEE co-treatment provokes perturbations in the autophagic mechanism of prostate cancer cells (PC-3) compared to DXR treatment alone, causing an excessive cell death. These findings propose the putative use of SEE as an adjuvant cytotoxic agent.

Knockdown of RNF2 enhances the radiosensitivity of squamous cell carcinoma in lung

2019 ◽  
Vol 97 (5) ◽  
pp. 589-599 ◽  
Author(s):  
Jie Yang ◽  
Fan Yu ◽  
Jinlei Guan ◽  
Tao Wang ◽  
Changjiang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
X Ray ◽  
Stable Transfectants

A previous study has reported that knockdown of RING finger protein 2 (RNF2) increases the radiosensitivity of esophageal cancer cells both in vitro and in vivo. However, the effect of RNF2 knockdown on radiosensitivity in squamous cell carcinoma (SqCC) remains unknown. For this, NCI-H226 and SK-MES-1 cells were exposed to X-ray irradiation and then RNF2 levels were determined. RNF2 was knocked-down and stable transfectants were selected. Radiosensitivity, cell proliferation, apoptosis, cell cycle, and γ-H2AX foci formation were evaluated. Interaction among ataxia telangiectasia mutated protein (ATM), mediator of DNA damage checkpoint 1 (MDC1), and H2AX were examined. Xenograft models were used to explore the effect of RNF2 knockdown on radiosensitivity in vivo. The results showed that RNF2 expression was significantly increased by X-ray irradiation. RNF2 knockdown combined with X-ray irradiation markedly inhibited cell proliferation, caused cell cycle arrest at the G1 phase, and induced cell apoptosis. In addition, RNF2 knockdown enhanced the radiosensitivity of SqCC cells, inhibited irradiation-induced γ-H2AX foci formation, and impaired the interactions among ATM, MDC1, and H2AX. Furthermore, combination of RNF2 knockdown and X-ray irradiation suppressed tumor growth and promoted tumor cell apoptosis in vivo. RNF2 may be a new therapeutic target to enhance the radiosensitivity of SqCC cells in lung.

scholarly journals SD-208, a Novel Protein Kinase D Inhibitor, Blocks Prostate Cancer Cell Proliferation and Tumor Growth In Vivo by Inducing G2/M Cell Cycle Arrest

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119346 ◽  
Author(s):  
Manuj Tandon ◽  
Joseph M. Salamoun ◽  
Evan J. Carder ◽  
Elisa Farber ◽  
Shuping Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Prostate Cancer Cell ◽  
Protein Kinase D ◽  
Cancer Cell Proliferation ◽  
M Cell ◽  
Cycle Arrest ◽  
Novel Protein

scholarly journals Polyphyllin I Promoted Melanoma Cells Autophagy and Apoptosis via PI3K/Akt/mTOR Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jianwen Long ◽  
Xianming Pi
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Melanoma Cell ◽  
Cell Apoptosis ◽  
Signal Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
A375 Cells

To investigate whether Polyphyllin I (PPI) might induce the autophagy and apoptosis of melanoma cells by regulating PI3K/Akt/mTOR signal pathway. Melanoma A375 cells were incubated with different concentrations of Polyphyllin I (0, 1.5, 3.0, and 6.0 mg/L) and PI3K/Akt/mTOR signaling pathway activator IGF-1(20 mg/L). CCK-8 assay was utilized to detect cell proliferation; Cell apoptosis and cell cycle were measured by flow cytometry; Western blot was used to examine the expressions of proteins. Immunofluorescence analysis was performed to evaluate autophagy of A375 cells; In addition, xenograft-bearing nude mice were applied to study the role of Polyphyllin I on melanoma development, melanoma cell proliferation, as well as melanoma cell apoptosis in vivo. The outcomes represented that Polyphyllin I promoted A375 cell apoptosis via upregulating Bax level and cleaved caspase-3 level and downregulating Bcl-2 level, inhibited the growth of A375 cells at the G0/G1 phase, and enhanced cell autophagy via regulating the levels of Beclin 1, LC3II, and p62. However, IGF-1 (an activator of PI3K/Akt/mTOR signal pathway) attenuated these changes that Polyphyllin I induced. Furthermore, the xenograft model experiment confirmed that Polyphyllin I treatment suppressed xenograft tumor growth, increased apoptotic index evaluated by the TUNEL method, and reduced the level of Ki67 in tumor tissues in vivo. In conclusion, Polyphyllin I treatment enhanced melanoma cell autophagy and apoptosis, as well as blocked melanoma cell cycle via suppressing PI3K/Akt/mTOR signal pathway. Meanwhile, Polyphyllin I treatment suppressed the development of melanoma in vivo. Therefore, Polyphyllin I possibly is a promising molecular targeted agent used in melanoma therapy.

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