Cellular Basis of Organotin(IV) Derivatives as Anticancer Metallodrugs: A Review

Organotin(IV) compounds have wide applications in industrial and agricultural fields owing to their ability to act as poly(vinyl chloride) stabilizers and catalytic agents as well as their medicinal properties. Moreover, organotin(IV) compounds may have applications as antitumor, anti-inflammatory, antifungal, or antimicrobial agents based on the observation of synergistic effects following the binding of their respective ligands, resulting in the enhancement of their biological activities. In this review, we describe the antiproliferative activities of organotin(IV) compounds in various human cancer cell lines based on different types of ligands. We also discuss the molecular mechanisms through which organotin(IV) compounds induce cell death via apoptosis through the mitochondrial intrinsic pathway. Finally, we present the mechanisms of cell cycle arrest induced by organotin(IV) compounds. Our report provides a basis for studies of the antitumor activities of organotin(IV) compounds and highlights the potential applications of these compounds as anticancer metallodrugs with low toxicity and few side effects.

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New Molecular Mechanisms and Clinical Impact of circRNAs in Human Cancer

Cancers ◽

10.3390/cancers13133154 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3154

Author(s):

Giulia Fontemaggi ◽

Chiara Turco ◽

Gabriella Esposito ◽

Silvia Di Agostino

Keyword(s):

Protein Interactions ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Human Cancer ◽

Biological Activities ◽

Circular Rnas ◽

Mesenchymal Transition ◽

Rna Molecules ◽

Cell Functions ◽

Ability To Act

Next generation RNA sequencing techniques, implemented in the recent years, have allowed us to identify circular RNAs (circRNAs), covalently closed loop structures resulting in RNA molecules that are more stable than linear RNAs. This class of non-coding RNA is emerging to be involved in a variety of cell functions during development, differentiation, and in many diseases, including cancer. Among the described biological activities, circRNAs have been implicated in microRNA (miRNA) sequestration, modulation of protein–protein interactions and regulation of mRNA transcription. In human cancer, circRNAs were implicated in the control of oncogenic activities such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. The most widely described mechanism of action of circRNAs is their ability to act as competing endogenous RNAs (ceRNAs) for miRNAs, lncRNAs and mRNAs, thus impacting along their axis, despite the fact that a variety of additional mechanisms of action are emerging, representing an open and expanding field of study. Furthermore, research is currently focusing on understanding the possible implications of circRNAs in diagnostics, prognosis prediction, effectiveness of therapies and, eventually, therapeutic intervention in human cancer. The purpose of this review is to discuss new knowledge on the mechanisms of circRNA action, beyond ceRNA, their impact on human cancer and to dissect their potential value as biomarkers and therapeutic targets.

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Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms

Molecules ◽

10.3390/molecules27010284 ◽

2022 ◽

Vol 27 (1) ◽

pp. 284

Author(s):

Abdelhakim Bouyahya ◽

Aicha El Allam ◽

Ikrame Zeouk ◽

Douae Taha ◽

Gokhan Zengin ◽

...

Keyword(s):

Human Cancer ◽

Human Cancer Cell Lines ◽

Beneficial Effects ◽

Human Cancer Cells ◽

Pharmaceutical Application ◽

Cycle Arrest ◽

Ability To Act ◽

Anti Cancer

Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.

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Synthesis of pyranopyrazolo N-glycoside and pyrazolopyranopyrimidine C-glycoside derivatives as promising antitumor and antimicrobial agents

Acta Pharmaceutica ◽

10.1515/acph-2015-0022 ◽

2015 ◽

Vol 65 (3) ◽

pp. 215-233 ◽

Cited By ~ 7

Author(s):

Hend N. Hafez ◽

Abdel-Rhman B. A. El-Gazzar

Keyword(s):

Antimicrobial Agents ◽

Human Cancer ◽

Biological Activities ◽

Systematic Investigation ◽

Reference Drug ◽

Human Cancer Cell Lines ◽

Gram Positive Bacteria ◽

Excellent Activity ◽

Antitumor Evaluation

Abstract As a part of systematic investigation of the synthesis and biological activities of pyrazole analogues linked to various heterocyclic systems, a new series of pyrazolo-N-glycoside derivatives, pyrazolopyranopyrimidine and C-glycoside of pyrazolopyranotriazolo-pyrimidine derivatives was synthesized through the reaction of the key intermediate 6-amino-3-methyl-4-(substituted-phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3a,b) with different reagents. Structures of the newly synthesized compounds were elucidated by elemental microanalysis and spectroscopic methods. The compounds were subjected to in vitro antitumor evaluation using the MTT assay. N-(β-D-ribofuranosyl)- and N-(β-D-xylofuranosyl)-6{[(1E)-4-chlorophenyl)-methylene] amino}4-(4-florophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile (6a,b) were the most active compounds against three human cancer cell lines. Also, most of the newly synthesized compounds exhibited high activity towards Gram-negative and Gram-positive bacteria. Compound 6a exhibited excellent activity towards bacteria compared to ofloxacine as the reference drug.

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In vitro studies of the anticancer action of Tectaria cicutaria in human cancer cell lines: G0/G1 p53-associated cell cycle arrest-Part I

Journal of Traditional and Complementary Medicine ◽

10.1016/j.jtcme.2017.07.003 ◽

2018 ◽

Vol 8 (4) ◽

pp. 459-464 ◽

Cited By ~ 2

Author(s):

Preeti Gajendra Karade ◽

Namdeo Ramhari Jadhav

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

In Vitro Studies ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Cycle Arrest

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Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer

Clinical medicine Oncology ◽

10.4137/cmo.s548 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S548 ◽

Cited By ~ 2

Author(s):

Takayuki Sugiyama ◽

Donna P. Frazier ◽

Pankaj Taneja ◽

Robert D. Kendig ◽

Rachel L. Morgan ◽

...

Keyword(s):

Transcription Factor ◽

Human Cancer ◽

Synergistic Effects ◽

Tumor Formation ◽

Binding Property ◽

Lung Cancers ◽

Myc Oncogene ◽

Oncogenic Ras ◽

Cycle Arrest ◽

Dependent Cell

Summary Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a transcription factor that has been isolated in a yeast two-hybrid screen through its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf promoter and induces Arf-p53-dependent cell cycle arrest in primary cells. D-type cyclins usually inhibit Dmp1-mediated transcription in a Cdk-independent fashion; however, Dmp1 shows synergistic effects with D-cyclins on the Arf promoter. Ras or Myc oncogene-induced tumor formation is accelerated in both Dmp1+/- and Dmp1-/- mice with no significant differences between Dmp1+/- and Dmp1-/-. Thus, Dmp1 is haplo-insufficient for tumor suppression. Tumors from Dmp1-/- or Dmp1+/- mice often retain wild-type Arf and p53, suggesting that Dmp1 is a physiological regulator of the Arf-p53 pathway. The Dmp1 promoter is activated by oncogenic Ras-Raf signaling, while it is repressed by physiological mitogenic stimuli, overexpression of E2F proteins, and genotoxic stimuli mediated by NF-κB. The human DMP1 gene (h DMP1) is located on chromosome 7q21 and is hemizygously deleted in approximately 40% of human lung cancers, especially those that retain normal INK4a/ARF and P53 loci. Thus, h DMP1 is clearly involved in human carcinogenesis, and tumors with h DMP1 deletion may constitute a discrete disease entity.

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Anti-Cancerous Potential of Polysaccharide Fractions Extracted from Peony Seed Dreg on Various Human Cancer Cell Lines Via Cell Cycle Arrest and Apoptosis

Frontiers in Pharmacology ◽

10.3389/fphar.2017.00102 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 10

Author(s):

Fang Zhang ◽

Jun-Jun Shi ◽

Kiran Thakur ◽

Fei Hu ◽

Jian-Guo Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Cycle Arrest

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CRISPR enriches for cells with mutations in a p53-related interactome, and this can be inhibited

10.1101/2021.03.10.434760 ◽

2021 ◽

Author(s):

Long Jiang ◽

Katrine Ingelshed ◽

Yunbing Shen ◽

Sanjaykumar V. Boddul ◽

Vaishnavi Srinivasan Iyer ◽

...

Keyword(s):

Cellular Response ◽

Human Cancer ◽

Genetic Alterations ◽

Dna Breaks ◽

Data Set ◽

Human Cancer Cell Lines ◽

Cycle Arrest ◽

Double Stranded Dna ◽

A Cell

CRISPR/Cas9 can be used to inactivate or modify genes by inducing double-stranded DNA breaks1–3. As a protective cellular response, DNA breaks result in p53-mediated cell cycle arrest and activation of cell death programs4,5. Inactivating p53 mutations are the most commonly found genetic alterations in cancer, highlighting the important role of the gene6–8. Here, we show that cells deficient in p53, as well as in genes of a core CRISPR-p53 tumor suppressor interactome, are enriched in a cell population when CRISPR is applied. Such enrichment could pose a challenge for clinical CRISPR use. Importantly, we identify that transient p53 inhibition suppresses the enrichment of cells with these mutations. Furthermore, in a data set of >800 human cancer cell lines, we identify parameters influencing the enrichment of p53 mutated cells, including strong baseline CDKN1A expression as a predictor for an active CRISPR-p53 axis. Taken together, our data identify strategies enabling safe CRISPR use.

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Oleiferasaponin C6 from the seeds of Camellia oleifera Abel.: a novel compound inhibits proliferation through inducing cell-cycle arrest and apoptosis on human cancer cell lines in vitro

RSC Advances ◽

10.1039/c6ra14467e ◽

2016 ◽

Vol 6 (94) ◽

pp. 91386-91393 ◽

Cited By ~ 10

Author(s):

Jianfa Zong ◽

Dongxu Wang ◽

Weiting Jiao ◽

Liang Zhang ◽

Guanhu Bao ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Camellia Oleifera ◽

Human Cancer Cell Lines ◽

Cycle Arrest

Oleiferasaponin C6 was isolated from Camellia oleifera Abel. and inhibits proliferation through inducing cell-cycle arrest and apoptosis on cancer cell lines in vitro.

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Biological Activity and Chemical Constituents of Essential Oil and Extracts of Murraya microphylla

Natural Product Communications ◽

10.1177/1934578x1501000935 ◽

2015 ◽

Vol 10 (9) ◽

pp. 1934578X1501000

Author(s):

Hai-Ning Lv ◽

Ke-Wu Zeng ◽

Bing-Yu Liu ◽

Yun Zhang ◽

Peng-Fei Tu ◽

...

Keyword(s):

Essential Oil ◽

Human Cancer ◽

Biological Activities ◽

Chemical Constituents ◽

Cytotoxic Activities ◽

Active Components ◽

Human Cancer Cell Lines ◽

Total Oil ◽

Promising Development ◽

Carbazole Alkaloids

Murraya microphylla is the most closely related species to M. koenigii (Curry tree). Inspired by the traditional effects of M. koenigii, the antioxidant, anti-inflammatory, and cytotoxic activities of the essential oil and extracts of M. microphylla were evaluated for the first time. The light petroleum and chloroform extracts were found to be able to scavenge DPPH free radicals, inhibit linoleic acid peroxidation, and nitric oxide production, as well as to present cytotoxicity to the human cancer cell lines HepG2, Bel7402, Bel7403, and Hela, but the essential oil only showed moderate activities. Chemical analysis of the active extracts by LC-DAD-MSn indicated that carbazole alkaloids were the main constituents. GC-MS analysis of the essential oil resulted in identification of 91 constituents, representing 96.9% of the total oil, with ( E)-caryophyllene (18.4%) and terpinen-4-ol (12.6%) as the major constituents. These results demonstrate that M. microphylla has similar biological activities, as well as chemical constituents to M. koenigii, and the carbazole alkaloids were disclosed to be the main potential active components. A promising development as a flavor and potential therapeutic agent could thus be predicated for this plant.

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