scholarly journals The Cardiac Glycoside Deslanoside Exerts Anticancer Activity in Prostate Cancer Cells by Modulating Multiple Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5809
Author(s):  
Mingcheng Liu ◽  
Qingqing Huang ◽  
Jun A ◽  
Linyue Li ◽  
Xiawei Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cardiac Glycoside ◽  
Cardiac Glycosides ◽  
Disease Free Survival ◽  
Diverse Range ◽  
Multiple Signaling

Prostate cancer (PCa) is a leading cause of cancer-related deaths among men worldwide, and novel therapies for advanced PCa are urgently needed. Cardiac glycosides represent an attractive group of candidates for anticancer repurposing, but the cardiac glycoside deslanoside has not been tested for potential anticancer activity so far. We found that deslanoside effectively inhibited colony formation in vitro and tumor growth in nude mice of PCa cell lines 22Rv1, PC-3, and DU 145. Such an anticancer activity was mediated by both the cell cycle arrest at G2/M and the induction of apoptosis, as demonstrated by different functional assays and the expression status of regulatory proteins of cell cycle and apoptosis in cultured cells. Moreover, deslanoside suppressed the invasion and migration of PCa cell lines. Genome-wide expression profiling and bioinformatic analyses revealed that 130 genes were either upregulated or downregulated by deslanoside in both 22Rv1 and PC-3 cell lines. These genes enriched multiple cellular processes, such as response to steroid hormones, regulation of lipid metabolism, epithelial cell proliferation and its regulation, and negative regulation of cell migration. They also enriched multiple signaling pathways, such as necroptosis, MAPK, NOD-like receptor, and focal adhesion. Survival analyses of the 130 genes in the TCGA PCa database revealed that 10 of the deslanoside-downregulated genes (ITG2B, CNIH2, FBF1, PABPC1L, MMP11, DUSP9, TMEM121, SOX18, CMPK2, and MAMDC4) inversely correlated, while one deslanoside-upregulated gene (RASD1) positively correlated, with disease-free survival in PCa patients. In addition, one deslanoside-downregulated gene (ENG) inversely correlated, while three upregulated genes (JUN, MXD1, and AQP3) positively correlated with overall survival in PCa patients. Some of the 15 genes have not been implicated in cancer before. These findings provide another candidate for repurposing cardiac glycosides for anticancer drugs. They also suggest that a diverse range of molecular events underlie deslanoside’s anticancer activity in PCa cells.

Synthesis, Spectral Characterization, Antibacterial and Anticancer Activity of some Titanium Complexes

2018 ◽  
Vol 18 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Raj Kaushal ◽  
Nitesh Kumar ◽  
Archana Thakur ◽  
Kiran Nehra ◽  
Pamita Awasthi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Spectral Characterization ◽  
Mechanistic Study ◽  
Titanium Complexes ◽  
G0 Phase ◽  
Antibacterial And Anticancer Activity ◽  
Dose Dependent

Abstract: Background: After the discovery of cisplatin, first non platinum anticancer drugs having excellent efficacy were budotitane and TiCl2(cp)2 but action mechanism is not clear. Therefore, we hereby reporting synthesis and biological activities novel titanium complexes to explore their mode of action. Objectives: Synthesis, spectral characterization, antibacterial and anticancer activity of some titanium complexes. Antibacterial studies on various bacterial strains and anticancer studies on HeLa, C6, CHO cancerous cell lines have been performed. Further, the cell death mechanistic study was done on CHO cell lines. Method: Titanium complexes with and without labile groups have been synthesized by reacting of TiCl4 with nitrogen containing ligands viz. 1,2-diaminocyclohexane, 1,10-Phenanthroline, adamantylamine, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine in predetermined molar ratios. Antibacterial and anticancer studies were performed by agar well diffusion method and MTT assay respectively. Cell cycle analysis is done by using flow cytometry. Results: Complex 2 i.e TiCl2(Phen)2 showed better activity than other complexes as an antibacterial as well as anticancer agent. Phase contrast imaging indicates that observed morphological changes of cells was dose dependent. Cell death mechanistic study have shown the increase in sub G0 phase population as well as formation of blebbing and fragmentation of chromatin material which is an indicative measure of apoptosis. Conclusion: Complex 2 proved to be more effective bactericide and cytotoxic agent. Cell cycle analysis showed cell arrest in G0 phase. Apoptosis percentage was found to increase in a dose dependent manner. So, prepared titanium complexes can be put to use as an important chemotherapeutic agents.

Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines

Gene ◽  
2019 ◽  
Vol 687 ◽  
pp. 261-271 ◽  
Author(s):  
Zeynep Özlem Doğan Şiğva ◽  
Tuğçe Balci Okcanoğlu ◽  
Çığır Biray Avci ◽  
Sunde Yilmaz Süslüer ◽  
Çağla Kayabaşi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Plant Extracts ◽  
Prostate Cancer Cell ◽  
Synergistic Effects ◽  
Signal Pathways ◽  
Endemic Plant ◽  
Prostate Cancer Cell Lines

scholarly journals Synthesis of Novel 2-Thioxothiazolidin-4-one and Thiazolidine-2, 4-dione Derivatives as Potential Anticancer Agents

2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
Alleni Suman Kumar ◽  
Rathod Aravind Kumar ◽  
Elala Pravardhan Reddy ◽  
Vavilapalli Satyanarayana ◽  
Jajula Kashanna ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Preliminary Data ◽  
Cancer Cell Lines ◽  
Structure Evolution ◽  
Model Compounds ◽  
Diverse Range ◽  
Novel Method

A variety of novel thiazolidine derivatives (2-thioxothiazolidin-4-one and thiazolidine-2, 4-dione derivatives) have been prepared by using 2,4-diphenyl-2 H-chromene-3-carbaldehyde and its derivatives as starting materials. This is the first example of the preparation of thiazolidine derivatives through this novel method. Structure evolution of the resulting thiazolidine derivatives leads to anticancer agents. Our preliminary data for some model compounds on three cancer cell lines (MCF7, A549 and B-16) suggested reasonable anticancer activity against the A549 and B-16 cell lines, with IC50 values of 20.7 and 20.4 μM, respectively. This method is operationally simple and works with a diverse range of substrates.

scholarly journals Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chao Hu ◽  
Xiaobin Zhu ◽  
Taogen Zhang ◽  
Zhouming Deng ◽  
Yuanlong Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Src Kinase ◽  
Akt Signaling ◽  
Cellular Level ◽  
Tanshinone Iia

Introduction. Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis in vitro, but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect. Materials and Methods. Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested in vitro. The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray. Results. The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. Conclusion. Tanshinone IIA plays an antiosteosarcoma role in vitro and in vivo and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.

scholarly journals Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines

2012 ◽  
Vol 13 (10) ◽  
pp. 5131-5136 ◽  
Author(s):  
Aied M. Alabsi ◽  
Rola Ali ◽  
Abdul Manaf Ali ◽  
Sami Abdo Radman Al-Dubai ◽  
Hazlan Harun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Apoptosis Induction ◽  
Cycle Arrest

scholarly journals Effect of Piceatannol on Cell Cycle Progression in Prostate Cancer Cells (P05-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Larissa Kido ◽  
Eun-Ryeong Hahm ◽  
Valeria Cagnon ◽  
Mário Maróstica ◽  
Shivendra Singh
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Cell Cycle Distribution ◽  
Mutant P53 ◽  
Wild Type ◽  
Cycle Progression ◽  
Cycle Arrest

Abstract Objectives Piceatannol (PIC) is a polyphenolic and resveratrol analog that is found in many vegetables consumed by humans. Like resveratrol, PIC has beneficial effects on health due to its anti-inflammatory, anti-oxidative and anti-proliferative features. However, the molecular targets of PIC in prostate cancer (PCa), which is the second most common cancer in men worldwide, are still poorly understood. Preventing cancer through dietary sources is a promising strategy to control diseases. Therefore, the aim of present study was to investigate the molecular mechanistic of actions of PIC in PCa cell lines with different genetic background common to human prostate cancer. Methods Human PCa cell lines (PC-3, 22Rv1, LNCaP, and VCaP) were treated with different doses of PIC (5–40 µM) and used for cell viability assay, measurement of total free fatty acids (FFA) and lactate, and cell cycle distribution. Results PIC treatment dose- and time-dependently reduced viability in PC-3 (androgen-independent, PTEN null, p53 null) and VCaP cells (androgen-responsive, wild-type PTEN, mutant p53). Because metabolic alterations, such as increased glucose and lipid metabolism are implicated in pathogenesis of in PCa, we tested if PIC could affect these pathways. Results from lactate and total free fatty acid assays in VCaP, 22Rv1 (castration-resistant, wild-type PTEN, mutant p53), and LNCaP (androgen-responsive, PTEN null, wild-type p53) revealed no effect of PIC on these metabolisms. However, PIC treatment delayed cell cycle progression in G0/G1 phase concomitant with the induction of apoptosis in both LNCaP and 22Rv1 cells, suggesting that growth inhibitory effect of PIC in PCa is associated with cell cycle arrest and apoptotic cell death at least LNCaP and 22Rv1 cells. Conclusions While PIC treatment does not alter lipid or glucose metabolism, cell cycle arrest and apoptosis induction are likely important in anti-cancer effects of PIC. Funding Sources São Paulo Research Foundation (2018/09793-7).

scholarly journals Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 681 ◽  
Author(s):  
Phuong Doan ◽  
Aliyu Musa ◽  
Akshaya Murugesan ◽  
Vili Sipilä ◽  
Nuno R. Candeias ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Glioblastoma Multiforme ◽  
Cell Cycle Arrest ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cell Population ◽  
Significant Role ◽  
Dependent Manner ◽  
Cycle Arrest

Cancer stem cells (CSCs), a small subpopulation of cells existing in the tumor microenvironment promoting cell proliferation and growth. Targeting the stemness of the CSC population would offer a vital therapeutic opportunity. 3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP), a small synthetic phenol compound, is proposed to play a significant role in controlling the CSC proliferation and survival. We assessed the potential therapeutic effects of THTMP on glioblastoma multiforme (GBM) and its underlying mechanism in various signaling pathways. To fully comprehend the effect of THTMP on the CSCs, CD133+ GBM stem cell (GSC) and CD133- GBM Non-stem cancer cells (NSCC) population from LN229 and SNB19 cell lines was used. Cell cycle arrest, apoptosis assay and transcriptome analysis were performed for individual cell population. THTMP strongly inhibited NSCC and in a subtle way for GSC in a time-dependent manner and inhibit the resistance variants better than that of temozolomide (TMZ). THTMP arrest the CSC cell population at both G1/S and G2/M phase and induce ROS-mediated apoptosis. Gene expression profiling characterize THTMP as an inhibitor of the p53 signaling pathway causing DNA damage and cell cycle arrest in CSC population. We show that the THTMP majorly affects the EGFR and CSC signaling pathways. Specifically, modulation of key genes involved in Wnt, Notch and Hedgehog, revealed the significant role of THTMP in disrupting the CSCs’ stemness and functions. Moreover, THTMP inhibited cell growth, proliferation and metastasis of multiple mesenchymal patient-tissue derived GBM-cell lines. THTMP arrests GBM stem cell cycle through the modulation of EGFR and CSC signaling pathways.

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