scholarly journals Mi-RNA-888-5p Is Involved in S-Adenosylmethionine Antitumor Effects in Laryngeal Squamous Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3665 ◽  
Author(s):  
Martina Pagano ◽  
Laura Mosca ◽  
Francesca Vitiello ◽  
Concetta Paola Ilisso ◽  
Alessandra Coppola ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Molecular Mechanisms ◽  
Mirna Expression Profile ◽  
Ros Generation ◽  
Antitumor Effects ◽  
Squamous Cancer ◽  
Consistent Increase ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Therapeutic Compound

(1) Purpose: The methyl donor S-Adenosylmethionine (AdoMet) has been widely explored as a therapeutic compound, and its application-alone or in combination with other molecules-is emerging as a potential effective strategy for the treatment and chemoprevention of tumours. In this study, we investigated the antitumor activity of AdoMet in Laryngeal Squamous Cell Carcinoma (LSCC), exploring the underlying mechanisms. (2) Results: We demonstrated that AdoMet induced ROS generation and triggered autophagy with a consistent increase in LC3B-II autophagy-marker in JHU-SCC-011 and HNO210 LSCC cells. AdoMet induced ER-stress and activated UPR signaling through the upregulation of the spliced form of XBP1 and CHOP. To gain new insights into the molecular mechanisms underlying the antitumor activity of AdoMet, we evaluated the regulation of miRNA expression profile and we found a downregulation of miR-888-5p. We transfected LSCC cells with miR-888-5p inhibitor and exposed the cells to AdoMet for 48 and 72 h. The combination of AdoMet with miR-888-5p inhibitor synergistically induced both apoptosis and inhibited cell migration paralleled by the up-regulation of MYCBP and CDH1 genes and of their targets. (3) Conclusion: Overall, these data highlighted that epigenetic reprogramming of miRNAs by AdoMet play an important role in inhibiting apoptosis and migration in LSCC cell lines.

Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3887-3898 ◽  
Author(s):  
Claudia Cocco ◽  
Sara Canale ◽  
Chiara Frasson ◽  
Emma Di Carlo ◽  
Emanuela Ognio ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Antitumor Activity ◽  
Molecular Mechanisms ◽  
Lymphoblastic Leukemia ◽  
Antitumor Agent ◽  
Underlying Mechanisms ◽  
Interleukin 23 ◽  
Novel Drug

Abstract Interleukin (IL)–23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23–induced up-regulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards.

scholarly journals Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis

2019 ◽  
Vol 20 (14) ◽  
pp. 3590 ◽  
Author(s):  
Michael A. Moses ◽  
Andrea L. George ◽  
Nozomi Sakakibara ◽  
Kanwal Mahmood ◽  
Roshini M. Ponnamperuma ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Squamous Epithelium ◽  
Critical Role ◽  
Multiple Organ ◽  
Stem Cell Marker ◽  
Basal Cells ◽  
Cancer Pathogenesis ◽  
Squamous Cancer ◽  
Epidermal Homeostasis ◽  
And Migration

The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.

scholarly journals Curcumin derivative WZ35 inhibits tumor cell growth via ROS-YAP-JNK signaling pathway in breast cancer

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Lihua Wang ◽  
Canwei Wang ◽  
Zheying Tao ◽  
Liqian Zhao ◽  
Zheng Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Ros Generation ◽  
Antitumor Effects ◽  
Jnk Activation

Abstract Background Breast cancer is the most prevalent cancer among women worldwide. WZ35, an analog of curcumin, has been demonstrated to remarkably improve the pharmacokinetic profiles in vivo compared with curcumin. WZ35 exhibits promising antitumor activity in gastric cancer, HCC, colon cancer. However, antitumor effects of WZ35 in breast cancer and its underlying molecular mechanisms remain unclear. Methods CCK8, Flow cytometry and transwell assays were used to measure cell proliferation, cell cycle arrest, apoptosis, cell migration and invasion. We constructed xenograft mouse model and lung metastasis model to assess the antitumor activities of WZ35 in vivo. To explore the underlying molecular mechanisms of WZ35, we performed a series of overexpression and knockdown experiments. The cellular oxygen consumption rates (OCRs) was measured to assess mitochondrial dysfunction. Results We found that treatment of breast cancer cells with WZ35 exerts stronger anti-tumor activities than curcumin both in vitro and in vivo. Mechanistically, our research showed that WZ35 induced reactive oxygen species (ROS) generation and subsequent YAP mediated JNK activation in breast cancer cells. Abrogation of ROS production markedly attenuated WZ35 induced anti-tumor activities as well as YAP and JNK activation. In addition, ROS mediated YAP and JNK activation induced mitochondrial dysfunction in breast cancer cells. Conclusion Our study showed that novel anti-cancer mechanisms of WZ35 in breast cancer cells and ROS-YAP-JNK pathway might be a potential therapeutic target for the treatment of breast cancer patients.

scholarly journals Antitumor Effects of 5-Aminolevulinic Acid on Human Malignant Glioblastoma Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5596
Author(s):  
Mohammad Jalili-Nik ◽  
Farzaneh Abbasinezhad-moud ◽  
Sajad Sahab-Negah ◽  
Abolfazl Maghrouni ◽  
Mohammad Etezad Razavi ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Ros Generation ◽  
Therapeutic Approaches ◽  
Antitumor Effects ◽  
Migration Ability ◽  
Cytotoxic Effects ◽  
Naturally Occurring ◽  
And Migration ◽  
Nih 3T3 ◽  
Different Doses

5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5-ALA exerted cytotoxic effects on GBM cells. We assessed cell viability, apoptosis rate, mRNA expressions of various apoptosis-related genes, generation of reactive oxygen species (ROS), and migration ability of the human U-87 malignant GBM cell line (U87MG) treated with 5-ALA at different doses. The half-maximal inhibitory concentration of 5-ALA on U87MG cells was 500 μg/mL after 7 days; 5-ALA was not toxic for human optic cells and NIH-3T3 cells at this concentration. The application of 5-ALA led to a significant increase in apoptotic cells, enhancement of Bax and p53 expressions, reduction in Bcl-2 expression, and an increase in ROS generation. Furthermore, the application of 5-ALA increased the accumulation of U87MG cells in the SUB-G1 population, decreased the expression of cyclin D1, and reduced the migration ability of U87MG cells. Our data indicate the potential cytotoxic effects of 5-ALA on U87MG cells. Further studies are required to determine the spectrum of the antitumor activity of 5-ALA on GBM.

scholarly journals miR-100 Suppresses the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma Cells via Targeting CXCR7

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yiman Ge ◽  
Jia Shu ◽  
Gang Shi ◽  
Fuguo Yan ◽  
Yejing Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Antitumor Effects ◽  
Hepatocellular Carcinoma Cells ◽  
Invasion And Migration ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Endothelial Growth Factor

This study is to elucidate the functions of miR-100 in hepatocellular carcinoma progression and to explore the underlying mechanisms. Expression levels of miR-100 in normal-cancer hepatocellular carcinoma tissues were measured using quantitative real-time PCR (qRT-PCR). The invasive and proliferative abilities of hepatocellular carcinoma cell lines transfected with mimic-NC or mimic-miR-100 were measured using transwell, CCK-8, and colony formation assays. The binding sites between CXCR7 and miR-100 were determined using luciferase reporter assays. The correlation of CXCR7 and miR-100 in hepatocellular carcinoma progression was further confirmed by cotransfection assays. Our results showed that miR-100 was significantly lower expressed in hepatocellular carcinoma tissues and negatively associated with CXCR7 expression. Cell functional assays’ results found that upregulation of miR-100 inhibited the proliferative, invasive, and migrative abilities in hepatocellular carcinoma cells. Luciferase reporter assay suggested that CXCR7 mRNA and miR-100 bound one another. Increasing CXCR7 expression reversed the inhibitive effects of upregulated miR-100 in hepatocellular carcinoma cells. Further study showed that miR-100/CXCR7 played a role in hepatocellular carcinoma progression by regulating metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF). Conclusively, miR-100 exerts antitumor effects on hepatocellular carcinoma. Overexpression of miR-100 attenuates the invasive and proliferative abilities of hepatocellular carcinoma cells by targeting CXCR7.

scholarly journals Pazopanib and Trametinib as a Synergistic Strategy against Osteosarcoma: Preclinical Activity and Molecular Insights

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1519
Author(s):  
Giulia Chiabotto ◽  
Giovanni Grignani ◽  
Maja Todorovic ◽  
Valentina Martin ◽  
Maria Laura Centomo ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Osteosarcoma Cell ◽  
Antitumor Effects ◽  
Interleukin 7 ◽  
Nanostring Technology

Receptor tyrosine kinases (RTKs) inhibitors’ activity in advanced osteosarcoma is significant but short-lived. To prevent or at least delay drug resistance, we explored a vertical inhibition by combining drugs acting at different levels of the RTK pathways (pazopanib + trametinib). We studied pazopanib + trametinib antitumor activity both in vitro and in vivo (MNNG-HOS and KHOS xenografts in NOD/SCID mice) investigating the molecular mechanisms and potential escapes. The involvement of MAPK-PI3K pathways was validated by Nanostring technology, western blot and by silencing/overexpression experiments. Pazopanib targets were expressed on seven osteosarcoma cell lines and their pathways were activated. Pazopanib + trametinib exhibited synergistic antitumor activity by inducing apoptosis and inhibiting ERK1/2 and Akt. In vivo antitumor activity was shown in osteosarcoma-bearing mice. The drug combination significantly down-modulated RTK Ephrin Type-A Receptor 2 (EphA2) and Interleukin-7 Receptor (IL-7R), whereas induced mitogen-activated protein-kinase kinase (MAPKK) MEK6. EphA2 silencing significantly reduced osteosarcoma cell proliferation and migration, while impeding MEK6 up-regulation in the treated cells significantly increased the antitumor effect of the studied drugs. Moreover, the up-regulation of MEK6 reduced combination activity. Pazopanib + trametinib demonstrated synergistic antitumor effects in osteosarcoma models through ERK and Akt inhibition and EphA2 and IL-7R down-modulation. MEK6 up-regulation might evoke escaping mechanism.

scholarly journals Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinghua Lv ◽  
Tianjiao Li ◽  
Manman Yang ◽  
Lihong Su ◽  
Zhendong Zhu ◽  
...  
Keyword(s):  
Reproductive System ◽  
Molecular Mechanisms ◽  
Dynamic Balance ◽  
Male Reproductive System ◽  
Ros Generation ◽  
Mitochondrial Dynamic ◽  
Chromium Vi ◽  
Underlying Mechanisms ◽  
Detoxification Process

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process in vivo. Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N6-methyladenosine (m6A) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA m6A modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA m6A modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.

scholarly journals Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway

2021 ◽  
Vol 7 ◽  
Author(s):  
Xinbing Sui ◽  
Xuemeng Han ◽  
Peng Chen ◽  
Qibiao Wu ◽  
Jiao Feng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Beneficial Effects ◽  
Cycle Arrest

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

scholarly journals Oxymatrine Inhibits Proliferation and Migration While Inducing Apoptosis in Human Glioblastoma Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Feili Liu ◽  
Baocheng Wang ◽  
Jiajia Wang ◽  
Xiaozheng Ling ◽  
Qifeng Li ◽  
...  
Keyword(s):  
Antitumor Effects ◽  
Human Glioblastoma ◽  
Anticancer Properties ◽  
Cell Proliferation And Migration ◽  
Associated Proteins ◽  
Screening Assays ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Mtt Assays ◽  
Proliferation And Migration

Oxymatrine (OMT), an alkaloid derived from the traditional Chinese medicine herb Sophora flavescens Aiton, has been shown to exhibit anticancer properties on various types of cancer cells. In this study, we investigate the anticancer properties of OMT on human glioblastoma (GBM) cells and evaluate their underlying mechanisms. MTT assays were performed and demonstrated that OMT significantly inhibits the proliferation of GBM cells. Flow cytometry suggested that OMT at a concentration of 10−5 M may induce apoptosis in U251 and A172 cells. Western blot analyses demonstrated a significant increase in the expression of Bax and caspase-3 and a significant decrease in expression of Bcl-2 in both U251 and A172 cells. Additionally, OMT was found by transwell and high-content screening assays to decrease the migratory ability of the evaluated GBM cells. These findings suggest that the antitumor effects of OMT may be the result of inhibition of cell proliferation and migration and the induction of apoptosis by regulating the expression of apoptosis-associated proteins. OMT may represent a novel anticancer therapy for the treatment of GBM.

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