Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/β-Catenin Signaling Pathway

Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway.

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Eupatilin Inhibits the Proliferation and Migration of Prostate Cancer Cells through Modulation of PTEN and NF-κB Signaling

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200811113549 ◽

2020 ◽

Vol 20 ◽

Author(s):

Riza Serttas ◽

Cagla Koroglu ◽

Suat Erdogan

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

And Migration ◽

Proliferation And Migration

Background: Despite advances in treatment of prostate cancer, side effects and the risks of developing drug resistance require new therapeutic agents. Eupatilin is a secondary metabolite of Artemisia asiatica and has shown potential anti-tumor activity in some cancers, but its potential in prostate cancer treatment has not yet been evaluated. Objective: The aim of the study was to investigate the effectiveness of eupatilin on prostate cancer cell proliferation and migration. Methods: Human prostate cancer PC3 and LNCaP cells were exposed to eupatilin and its efficacy on cell survival was determined by MTT test. Apoptosis and cell cycle phases were evaluated by image-based cytometer. Cell migration and invasion was evaluated by wound healing and matrigel migration assays; the expression of mRNA and protein were assessed by RT-qPCR and Western blot,respectively. Results: Eupatilin time- and dose-dependently reduced the viability of prostate cancer cells. Exposure of PC3 cells to 12.5 µM - 50 µM eupatilin resulted in apoptosis by upregulating the expression of caspase 3, Bax and cytochrome c. Annexin V assessment also confirmed that eupatilin causes apoptosis. The treatment significantly upregulated mRNA expression of p53, p21, and p27, causing cell cycle arrest in the G1 phase. Administration of eupatilin inhibited migration and invasion of the cells by down-regulating the expression of Twist, Slug and MMP-2, -7. In addition, the agent increased protein expression of tumor suppressor PTEN, while transcription factor NF-κB expression was reduced. Conclusion: Eupatilin strongly prevents proliferation of prostate cancer cells, and suppresses migration and invasion. Because of its therapeutic potential, the clinical use of eupatilin in prostate cancer should also be supported by in vivo studies.

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miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo

BMC Cancer ◽

10.1186/s12885-019-5819-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 10

Author(s):

Mirjam Kiener ◽

Lanpeng Chen ◽

Markus Krebs ◽

Joël Grosjean ◽

Irena Klima ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

And Migration ◽

Proliferation And Migration

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Role of MicroRNA-101 on Proliferation and Migration of Prostate Cancer Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2789 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2076-2080

Author(s):

Yiming Weng ◽

Jun Xiang ◽

Wei Le ◽

Yuanshen Mao

Keyword(s):

Prostate Cancer ◽

Control Groups ◽

Cancer Pathogenesis ◽

Pc3 Cells ◽

Cox 2 ◽

And Migration ◽

And Control ◽

Mtt Assays ◽

Proliferation And Migration

Background: MicroRNA-101 is a tumor inhibitor that stimulates tumor progression by reducing or inhibiting the expression of certain oncogenes. Some studies presented that cox-2 is target of MicroRNA 101 in prostate cancer process. Methods: MicroRNA-101 expression was detected by RT-PCR in PC3 cell lines. A and to determine cell proliferation we used MTT assays. Cell would heal and Flow cytometry assays were also used to detect cellular migratory ability and apoptosis, respectively. To assess cox-2 protein expression, Immunohistochemistry was used and data analyzed by data analysis by SPSS 20. Results: PC3 cells treated by MicroRNA-101 mimics displayed a 24% elevation in growth rate compared with blank (P < 0.01) at 48 h, and a 12% increase (P < 0.01) at 72 h. On the other hand, at 48 and 72 h after the MicroRNA-101 inhibitor transfection, proliferation of PC3 cell was decreased significantly. The early apoptosis rate in transfected PC3 cells with MicroRNA-101 mimic (74.4%) and inhibitor (22.8%) were significantly different at 72 h after transfection (P < 0.05), MicroRNA-101 mimics inhibited cell migration, adhesion, and spread was wider relative to the group of control and inhibitor for the PC3 cells. Expression of Cox-2 in transfected PC3 with the MicroRNA-101 inhibitor was higher than the mimic and control groups significantly (P < 0.01). Conclusion: MicroRNA-101 by Cox-2 can play key roles in the prostate cancer pathogenesis.

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MicroRNA‐139 is a predictor of prostate cancer recurrence and inhibits growth and migration of prostate cancer cells through cell cycle arrest and targeting IGF1R and AXL

The Prostate ◽

10.1002/pros.23871 ◽

2019 ◽

Vol 79 (12) ◽

pp. 1435-1451 ◽

Cited By ~ 11

Author(s):

Robert K. Nam ◽

Tania Benatar ◽

Christopher J. D. Wallis ◽

Elizabeth Kobylecky ◽

Yutaka Amemiya ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cancer Recurrence ◽

Prostate Cancer Cells ◽

Cycle Arrest ◽

Prostate Cancer Recurrence ◽

And Migration

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IGHG1 Regulates Prostate Cancer Growth via the MEK/ERK/c-Myc Pathway

BioMed Research International ◽

10.1155/2019/7201562 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Jing Chu ◽

Yutong Li ◽

Zhihai Deng ◽

Zhenlin Zhang ◽

Qun Xie ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Growth ◽

Heavy Chain ◽

Cancer Growth ◽

Prostate Cancer Cells ◽

Cycle Arrest ◽

Underlying Mechanisms

Increasing evidence indicates that immunoglobulins are important for the regulation of various cancers including prostate cancer (PCa). However, the underlying mechanisms of IgG regulated PCa development remain to be further explored. Here, we demonstrated that IgG1 heavy chain (IGHG1) was increased in tissues from PCa patients. Inhibition of IGHG1 by antibody blocking or genetic knockdown suppressed cell growth and induced cell cycle arrest and ultimate apoptosis. Expression levels of c-Myc were positively correlated with the levels of IGHG1. Furthermore, MEK/ERK/c-Myc pathway lied downstream of IGHG1 in cultured prostate cancer cells. Inhibition of IGHG1 restrained the tumor growth in nude mice and inactivated MEK/ERK/c-Myc pathway both in vitro and in vivo. These findings suggest that IGHG1 play a crucial role during the development of prostate cancer and inhibition of IGHG1 may be a potential therapy in the treatment of PCa.

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Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5591687 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jing Xie ◽

Lin-jie Peng ◽

Ming-rong Yang ◽

Wei-wei Jiang ◽

Jia-ying Mao ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Moringa Oleifera ◽

A549 Cells ◽

Cycle Arrest ◽

And Migration ◽

Related Proteins ◽

Moringa Oleifera Lam ◽

Proliferation And Migration

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

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Anti-Cancer Effects of Paris Polyphylla Ethanol Extract by Inducing Cancer Cell Apoptosis and Cycle Arrest in Prostate Cancer Cells

Current Urology ◽

10.1159/000447209 ◽

2017 ◽

Vol 11 (3) ◽

pp. 144-150 ◽

Cited By ~ 3

Author(s):

Denglu Zhang ◽

Kailin Li ◽

Chao Sun ◽

Guangshang Cao ◽

Yuanfu Qi ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Ethanol Extract ◽

Prostate Cancer Cells ◽

Cycle Arrest ◽

Paris Polyphylla ◽

Du145 Cells

Objective: To evaluate the potential anti-prostate cancer effects of Paris polyphylla ethanol extract (PPEE) and its underlying mechanisms. Materials and Methods: The anti-proliferation activity of PPEE was tested on PC3 and DU145 cells using Cell Counting Kit-8 assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by flow cytometry. Apoptosis of prostate cancer cells was induced by PPEE through endogenous and exogenous pathways. A mouse xenograft model was used to examine its anti-prostate cancer effects in vivo. Results: We found that the IC50 of PPEE on PC3 cells was 3.98 µg/ml and the IC50 of PPEE on DU145 cells was 8 µg/ml. PPEE induced prostate cancer cell apoptosis in a concentration dependent manner, through endogenous and exogenous pathways. PPEE induced PC3 cell cycle arrest in G0/G1 and G2/M phases, while in DU145cell it induced cell arrest in the G0/G1 phase. PPEE inhibited the growth of prostate cancer cells in vivo. Conclusion: PPEE could inhibit prostate cancer growth in vitro and in vivo, induce apoptosis of prostate cancer cells, and cause cell cycle arrest, which laid the foundation for further research on the anti-tumor mechanism of PPEE.

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Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa108 ◽

2020 ◽

Author(s):

Yuanyuan Wang ◽

Shanqi Guo ◽

Yingjie Jia ◽

Xiaoyu Yu ◽

Ruiyu Mou ◽

...

Keyword(s):

Prostate Cancer ◽

Flavonoid Compound ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Invasion And Migration ◽

Beneficial Effects ◽

Anticancer Properties ◽

Xenograft Models ◽

And Migration

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

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miR-636 inhibits EMT, cell proliferation and cell cycle of ovarian cancer by directly targeting transcription factor Gli2 involved in Hedgehog pathway

Cancer Cell International ◽

10.1186/s12935-020-01725-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiong Ma ◽

Chunxia Zhou ◽

Xuejun Chen

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Protein Expression ◽

Signaling Pathway ◽

Luciferase Reporter ◽

Cell Proliferation And Migration ◽

Hh Signaling ◽

And Migration ◽

Proliferation And Migration

Abstract Background Hedgehog (Hh) signaling pathway, which is essential for cell proliferation and differentiation, is noted to be aberrantly activated in tumor from increasing studies in recent years. MicroRNAs (miRNAs) as an important non-coding RNA in cells have been proven to possess a regulatory role specific to the Hh signaling pathway. Here, in vitro and in vivo cellular/molecular experiments were adopted to clarify the regulatory mechanism linking miR-636 to the Hh signaling pathway in ovarian cancer (OVC). Methods Protein–protein interaction analysis was performed to identify the hub gene in the Hh pathway. TargetScan database was used to predict the potential upstream regulators for Gli2. qRT-PCR was performed to test the expression of miR-636, while Western blot was conducted to detect the expression of proteins related to the Hh pathway and epithelial-mesenchymal transition (EMT). For cell functional experiments, HO-8910PM OVC cell line was used. MTT assay and wound healing assay were used to measure the effect of miR-636 on cell proliferation and migration. Flow cytometry was carried out to examine the effect of miR-636 on cell cycle, and Western blot was used to identify the change in expression of Hh and EMT-related proteins. Dual-luciferase reporter gene assay was implemented to detect the targeting relationship between miR-636 and Gli2. Xenotransplantation models were established for in vivo examination. Results Gli2 was identified as the hub gene of the Hh pathway and it was validated to be regulated by miR-636 based on the data from TargetScan and GEO databases. In vitro experiments discovered that miR-636 was significantly lowly expressed in OVC cell lines, and overexpressing miR-636 significantly inhibited HO-8910PM cell proliferation, migration and induced cell cycle arrest in G0/G1 phase, while the inhibition of miR-636 caused opposite results. Dual-luciferase reporter gene assay revealed that Gli2 was the target gene of miR-636 in OVC. Besides, overexpressed miR-636 decreased protein expression of Gli2, and affected the expression of proteins related to the Hh signaling pathway and EMT. Rescue experiments verified that overexpression of Gli2 reversed the inhibitory effect of miR-636 on HO-8910PM cell proliferation and migration, and attenuated the blocking effect of miR-636 on cell cycle. The xenotransplantation experiment suggested that miR-636 inhibited cell growth of OVC by decreasing Gli2 expression. Besides, overexpressing Gli2 potentiated the EMT process of OVC cells via decreasing E-cadherin protein expression and increasing Vimentin protein expression, and it reversed the inhibitory effect of miR-636 on OVC cell proliferation in vivo. Conclusion miR-636 mediates the activation of the Hh pathway via binding to Gli2, thus inhibiting EMT, suppressing cell proliferation and migration of OVC. Trial registration: The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of The Second Affiliated hospital of Zhejiang University School of Medicine (IR2019001235). Written informed consent was obtained from individual or guardian participants.

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