scholarly journals Corilagin in Cancer: A Critical Evaluation of Anticancer Activities and Molecular Mechanisms

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3399 ◽  
Author(s):  
Ashutosh Gupta ◽  
Amit Kumar Singh ◽  
Ramesh Kumar ◽  
Risha Ganguly ◽  
Harvesh Kumar Rana ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Critical Evaluation ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Altered Expression ◽  
Anticancer Efficacy ◽  
Extracellular Signal ◽  
M Phase ◽  
Induced Apoptosis

Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.

scholarly journals Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 191
Author(s):  
Ambre Dezaire ◽  
Christophe H. Marchand ◽  
Marine Vallet ◽  
Nathalie Ferrand ◽  
Soraya Chaouch ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Crude Extract ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Chemical Library ◽  
Altered Expression ◽  
Cancer Aggressiveness

High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.

scholarly journals Interferon α Induces Nucleus-independent Apoptosis by Activating Extracellular Signal-regulated Kinase 1/2 and c-Jun NH2-Terminal Kinase Downstream of Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin

2008 ◽  
Vol 19 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Theocharis Panaretakis ◽  
Linn Hjortsberg ◽  
Katja Pokrovskaja Tamm ◽  
Ann-Charlotte Björklund ◽  
Bertrand Joseph ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Interferon Α ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Induced Apoptosis ◽  
Phosphatidylinositol 3

Interferon (IFN)α induces apoptosis via Bak and Bax and the mitochondrial pathway. Here, we investigated the role of known IFNα-induced signaling cascades upstream of Bak activation. By pharmacological and genetic inhibition of the kinases protein kinase C (PKC)δ, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) in U266-1984 and RHEK-1 cells, we could demonstrate that all three enzymes are critical for the apoptosis-associated mitochondrial events and apoptotic cell death induced by IFNα, at a step downstream of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). Furthermore, the activation of JNK was found to occur in a PKCδ/ERK-dependent manner. Inhibition of these kinases did not affect the canonical IFNα-stimulated Janus tyrosine kinase-signal transducer and activator of transcription signaling or expression of IFN-responsive genes. Therefore, enucleated cells (cytoplasts) were examined for IFNα-induced apoptosis, to test directly whether this process depends on gene transcription. Cytoplasts were found to undergo apoptosis after IFNα treatment, as analyzed by several apoptosis markers by using flow cytometry, live cell imaging, and biochemical analysis of flow-sorted cytoplasts. Furthermore, inhibition of mTOR, ERK, and JNK blocked IFNα-induced apoptosis in cytoplasts. In conclusion, IFNα-induced apoptosis requires activation of ERK1/2, PKCδ, and JNK downstream of PI3K and mTOR, and it can occur in a nucleus-independent manner, thus demonstrating for the first time that IFNα induces apoptosis in the absence of de novo transcription.

Lycorine Modulates the Expression of p21 Via a p53-Independent Pathway in HL-60 Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4297-4297
Author(s):  
Jing Liu ◽  
Shu-Ling Wang ◽  
Lin Fang ◽  
Mao Ye ◽  
Zhi-Wei Sun ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Fold Increase ◽  
Alternative Pathways ◽  
Cyclin Dependent Kinase Inhibitor ◽  
M Phase ◽  
Induced Apoptosis

Abstract Abstract 4297 Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia is a common type of leukemia. We have previously shown that lycorine, a natural alkaloid extract from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. Lycorine treatment of HL-60 cell arrested cell cycle at G2/M phase and induced apoptosis. In the present study, we sought to explore the molecular mechanisms for the anti-leukemia action of lycorine. Gene chip analysis revealed that lycorine treatment of HL-60 cells induced more than 9 fold increase of p21, a cyclin-dependent kinase inhibitor, whose expression is mainly regulated by p53. Since HL-60 cells are p53 null, the above findings suggest that lycorine activates p21 expression through p53-independent pathway. To further explore the alternative pathways for the activation of p21 induced by lycorine, we examined the effect of lycorine on the expression of Rb, pRb, E2F, c-Myc and HDACs which have shown to regulate p21 expression. We show that expression of pRb (ser780) and c-Myc was down-regulated, Rb and E2F were up-regulated, while the expression of HDAC1 and HDAC3 was not changed. Together these findings suggest that lycorine exerts its anti-leukemia effect by activating p21 expression via pRb/E2F and c-Myc pathways. Disclosures: No relevant conflicts of interest to declare.

scholarly journals γ-Tocotrienol-induced apoptosis in human gastric cancer SGC-7901 cells is associated with a suppression in mitogen-activated protein kinase signalling

2008 ◽  
Vol 99 (6) ◽  
pp. 1247-1254 ◽  
Author(s):  
Wenguang Sun ◽  
Qi Wang ◽  
Bingqing Chen ◽  
Jiaren Liu ◽  
Huikun Liu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Signalling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Human Gastric Cancer ◽  
Down Regulation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Human Gastric Adenocarcinoma ◽  
Induced Apoptosis

Tocotrienols have been shown to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in tocotrienol-induced apoptosis are still unclear. In the present study, γ-tocotrienol induced apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down regulation of the extracellular signal-regulated kinase (ERK) signalling pathway. Furthermore, γ-tocotrienol-induced apoptosis was accompanied by down regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up or down regulation of Bcl-2 family proteins play a major role in the initiation of γ-tocotrienol-induced apoptosis as an activator of caspase-3.γ-Tocotrienol also down regulated the activation of the Raf-ERK signalling pathway, and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2 proteins. The results suggest that key regulators in tocotrienol-induced apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down regulation of the Raf-ERK signalling pathway.

The Local Anaesthetic Lignocaine Exhibits Potent Antilung Cancer Cell Activity by Inhibiting the Phosphoinositide 3-Kinases/Mammalian Target of Rapamycin/Mammalian Target of Rapamycin Pathway

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 139-146 ◽  
Author(s):  
Quanling Dong ◽  
Zhifu Mao
Keyword(s):  
Lung Cancer ◽  
Cancer Cell ◽  
Mammalian Target Of Rapamycin ◽  
Flow Cytometric Analysis ◽  
Cell Activity ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Target Of Rapamycin ◽  
Human Lung Carcinoma ◽  
Induced Apoptosis

We studied the effect of lignocaine (LIG) on lung cancer cells. LIG dose- and concentration-dependently reduced the viability of the lung cancer cell line 95D. Fluorescence microscopy revealed that LIG-induced apoptosis, and this was confirmed via flow cytometric analysis of cells treated with various concentrations of LIG; the drug increased the proportions of cells in S-phase. Bad and Bax levels rose, and that of Bcl2 fell significantly, after addition of LIG; Western blotting showed that the drug also reduced the levels of phosphorylated proteins involved in downstream phosphoinositide 3-kinases/mammalian target of rapamycin/mammalian target of rapamycin signaling. In conclusion, our results suggest that LIG may be a useful therapy for human lung carcinoma.

scholarly journals Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP+-Induced Apoptosis in a Cell Culture Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6422
Author(s):  
Qi Xu ◽  
Ziyu Chen ◽  
Borong Zhu ◽  
Yiming Li ◽  
Manju B. Reddy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Water Soluble ◽  
Cell Culture Model ◽  
Neuroprotective Effects ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Culture Model ◽  
A Cell ◽  
Induced Apoptosis ◽  
Soluble Components

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP+)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP+. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP+. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP+ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

scholarly journals The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis

2002 ◽  
Vol 157 (5) ◽  
pp. 761-770 ◽  
Author(s):  
Carine Bossenmeyer-Pourié ◽  
Rama Kannan ◽  
Stéphane Ribieras ◽  
Corinne Wendling ◽  
Isabelle Stoll ◽  
...  
Keyword(s):  
Phase Transition ◽  
Cell Differentiation ◽  
Tumor Suppressor ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Active Form ◽  
Suppressor Gene ◽  
Trefoil Factor ◽  
Altered Expression ◽  
Induced Apoptosis

Trefoil factor (TFF)1 is synthesized and secreted by the normal stomach mucosa and by the gastrointestinal cells of injured tissues. The link between mouse TFF1 inactivation and the fully penetrant antropyloric tumor phenotype prompted the classification of TFF1 as a gastric tumor suppressor gene. Accordingly, altered expression, deletion, and/or mutations of the TFF1 gene are frequently observed in human gastric carcinomas. The present study was undertaken to address the nature of the cellular and molecular mechanisms targeted by TFF1 signalling. TFF1 effects were investigated in IEC18, HCT116, and AGS gastrointestinal cells treated with recombinant human TFF1, and in stably transfected HCT116 cells synthesizing constitutive or doxycycline-induced human TFF1. We observed that TFF1 triggers two types of cellular responses. On one hand, TFF1 lowers cell proliferation by delaying G1-S cell phase transition. This results from a TFF1-mediated increase in the levels of cyclin-dependent kinase inhibitors of both the INK4 and CIP subfamilies, leading to lower E2F transcriptional activity. On the other hand, TFF1 protects cells from chemical-, anchorage-free–, or Bad-induced apoptosis. In this process, TFF1 signalling targets the active form of caspase-9. Together, these results provide the first evidence of a dual antiproliferative and antiapoptotic role for TFF1. Similar paradoxical functions have been reported for tumor suppressor genes involved in cell differentiation, a function consistent with TFF1.

scholarly journals Checking NEKs: Overcoming a Bottleneck in Human Diseases

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1778 ◽  
Author(s):  
Andressa Peres de Oliveira ◽  
Luidy Kazuo Issayama ◽  
Isadora Carolina Betim Pavan ◽  
Fernando Riback Silva ◽  
Talita Diniz Melo-Hanchuk ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Human Diseases ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Damage Response ◽  
Cilia Formation ◽  
Potential Applications ◽  
Phosphoinositide 3 Kinase

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as the cell cycle, cell division, cilia formation, and the DNA damage response. The review of the literature points to the pivotal participation of NEKs in important human diseases, like different types of cancer, diabetes, ciliopathies and central nervous system related and inflammatory-related diseases. The different known regulatory molecular mechanisms specific to each NEK are also presented, relating to their involvement in different diseases. In addition, important information about NEKs remains to be elucidated and is highlighted in this review, showing the need for other studies and research regarding this kinase family. Therefore, the NEK family represents an important group of kinases with potential applications in the therapy of human diseases.

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