scholarly journals Antitumor Potential of Marine and Freshwater Lectins

Marine Drugs ◽  
2019 ◽  
Vol 18 (1) ◽  
pp. 11 ◽  
Author(s):  
Elena Catanzaro ◽  
Cinzia Calcabrini ◽  
Anupam Bishayee ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Complete Healing ◽  
Anticancer Compounds ◽  
Freshwater Organisms ◽  
Regulated Cell Death ◽  
Antitumor Potential ◽  
Unique Source

Often, even the most effective antineoplastic drugs currently used in clinic do not efficiently allow complete healing due to the related toxicity. The reason for the toxicity lies in the lack of selectivity for cancer cells of the vast majority of anticancer agents. Thus, the need for new potent anticancer compounds characterized by a better toxicological profile is compelling. Lectins belong to a particular class of non-immunogenic glycoproteins and have the characteristics to selectively bind specific sugar sequences on the surface of cells. This property is exploited to exclusively bind cancer cells and exert antitumor activity through the induction of different forms of regulated cell death and the inhibition of cancer cell proliferation. Thanks to the extraordinary biodiversity, marine environments represent a unique source of active natural compounds with anticancer potential. Several marine and freshwater organisms, ranging from the simplest alga to the most complex vertebrate, are amazingly enriched in these proteins. Remarkably, all studies gathered in this review show the impressive anticancer effect of each studied marine lectin combined with irrelevant toxicity in vitro and in vivo and pave the way to design clinical trials to assess the real antineoplastic potential of these promising proteins. It provides a concise and precise description of the experimental results, their interpretation as well as the experimental conclusions that can be drawn.

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

Advances on Quinazoline Based Congeners for Anticancer Potential

2021 ◽  
Vol 25 ◽  
Author(s):  
Parul Grover ◽  
Monika Bhardwaj ◽  
Garima Kapoor ◽  
Lovekesh Mehta ◽  
Roma Ghai ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
Anticancer Compounds ◽  
In Vivo Models ◽  
Appropriate Treatment

: The heterocyclic compounds have a great significance in medicinal chemistry because they have extensive biological activities. Cancer is globally the leading cause of death and it is a challenge to develop an appropriate treatment for the management of cancer. Continuous efforts are being made to find a suitable medicinal agent for cancer therapy. Nitrogen-containing heterocycles have received noteworthy attention due to their wide and distinctive pharmacological activities. One of the most important nitrogen-containing heterocycles in medicinal chemistry is ‘quinazoline’ that possesses a wide spectrum of biological properties. This scaffold is an important pharmacophore and is considered a privileged structure. The various substituted quinazolines displayed anticancer activity against different types of cancer. This review highlights the recent advances in quinazoline based molecules as anticancer agents. Several in-vitro and in-vivo models used along with the results are also included. A subpart briefing natural quinazoline containing anticancer compounds is also incorporated in the review.

Current developments in the Pyran-Based Analogues as Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Parul Grover ◽  
Monika Bhardwaj ◽  
Lovekesh Mehta ◽  
Garima Kapoor ◽  
Pooja A. Chawla
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Anticancer Compounds ◽  
Appropriate Treatment ◽  
Anti Cancer ◽  
Privileged Structure ◽  
Different Types

: Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.‘Pyran’ is one of the most significant non-aromatic, six-membered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in-vitro (cell based testing), in-vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review.

scholarly journals Metadherin enhances vulnerability of cancer cells to ferroptosis

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Jianling Bi ◽  
Shujie Yang ◽  
Long Li ◽  
Qun Dai ◽  
Nicholas Borcherding ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Messenger Rna ◽  
Underlying Mechanism ◽  
Lipid Hydroperoxides ◽  
Protein Levels ◽  
Enhanced Sensitivity ◽  
Regulated Cell Death

Abstract Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death driven by lipid hydroperoxides within biological membranes. Although therapy-resistant mesenchymal-high cancers are particularly vulnerable to ferroptosis inducers, especially phospholipid glutathione peroxidase 4 (GPx4) inhibitors, the underlying mechanism is yet to be deciphered. As such, the full application of GPx4 inhibitors in cancer therapy remains challenging. Here we demonstrate that metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc− heterodimerization partner), at both the messenger RNA and protein levels. Our metabolomic studies demonstrated that MTDH reduced intracellular cysteine, but increased glutamate levels, ultimately decreasing levels of glutathione and setting the stage for increased vulnerability to ferroptosis. Finally, we observed an enhanced antitumor effect when we combined various ferroptosis inducers both in vitro and in vivo; the level of MTDH correlated with the ferroptotic effect. We have demonstrated for the first time that MTDH enhances the vulnerability of cancer cells to ferroptosis and may serve as a therapeutic biomarker for future ferroptosis-centered cancer therapy.

scholarly journals An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Syam Prakash Somasekharan ◽  
Amal El-Naggar ◽  
Poul H. Sorensen ◽  
Yuzhuo Wang ◽  
Hongwei Cheng
Keyword(s):  
Cancer Cells ◽  
Aqueous Extract ◽  
Anticancer Agents ◽  
Anticancer Activities ◽  
Antimetastatic Effect ◽  
Pancreatic Cancers ◽  
Subrenal Capsule ◽  
Nonadherent Cells

Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma.In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells.In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted.

scholarly journals Smart stimuli-responsive biofunctionalized niosomal nanocarriers for programmed release of bioactive compounds into cancer cells in vitro and in vivo

2021 ◽  
Vol 10 (1) ◽  
pp. 1895-1911
Author(s):  
Najmeh Alsadat Abtahi ◽  
Seyed Morteza Naghib ◽  
Fatemeh Haghiralsadat ◽  
Javad Zavar Reza ◽  
Fatemeh Hakimian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Tumor Model ◽  
Tween 80 ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Mouse Tumor ◽  
Transfection Efficacy

Abstract Cancer treatment is challenging due to late-stage diagnosis, drug resistance and systemic toxicity of chemotherapeutic agents. The formulation of the drug into nanoparticles (NPs) can enhance the treatment efficacy and effectiveness. Therefore, a new cationic niosomal formulation, which contains Tween 80, Tween 60, cholesterol and lysine amino acid as a platform model to enhance transfection efficacy and reach more acceptable stability, and curcumin (Cur) as a biological anti-cancer drug, are introduced. Here, the authors focused on the design and synthesis of novel lysine-mediated niosomal NPs for the effectual and controlled release of the antitumor agent, Cur, and turned to optimize niosome formulations, concerning the volume of cholesterol and surfactant to implement these anticancer agents, simultaneously. The characterization of NPs s was carried out and the results showed the successful synthesis of Cur-entrapped niosomal NPs with high efficacy, sufficient positive charges and a favorable size (95/33 nm). The in vitro studies have been performed to investigate the cytotoxicity, cellular uptake and apoptosis of normal and cancer cells treated by black niosome, free Cur and niosom-loaded Cur. The results showed that implementing agents by niosome caused enhanced cytotoxicity, uptake and anticancer activity in cancer cells in comparison with normal cells. Furthermore, the effect of this nanodrug was surveyed on the 4T1 xenografted Balb/C mouse tumor model. Cur delivery to cancer models caused a higher tumor inhibition rate than in other groups.

Indole alkaloids, synthetic dimers and hybrids with potential in vivo anticancer activity

2020 ◽  
Vol 20 ◽  
Author(s):  
Feng Song ◽  
Yunqiang Bian ◽  
Jing Liu ◽  
Zhenghua Li ◽  
Li Zhao ◽  
...  
Keyword(s):  
Organic Compound ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Indole Alkaloids ◽  
Structural Diversity ◽  
Therapeutic Application ◽  
Antiproliferative Effects ◽  
Therapeutic Properties

: Indole, a heterocyclic organic compound, is one of the most promising heterocycles found in natural and synthetic sources since its derivatives possess fascinating structural diversity and various therapeutic properties. Indole alkaloids, synthetic dimers and hybrids could act on diverse targets in cancer cells, and consequently possess potential antiproliferative effects on various cancers both in vitro and in vivo. Vinblastine, midostaurin, and anlotinib as the representative of indole alkaloids, synthetic dimers and hybrids respectively have already been clinically applied to treat many types of cancers, demonstrating indole alkaloids, synthetic dimers and hybrids are useful scaffolds for the development of novel anticancer agents. Covering articles published between 2010 and 2020, this review emphasizes the recent development of indole alkaloids, synthetic dimers and hybrids with potential in vivo therapeutic application for cancers.

scholarly journals Identification of a small-molecule compound that inhibits homodimerization of oncogenic NAC1 protein and sensitizes cancer cells to anticancer agents

2019 ◽  
Vol 294 (25) ◽  
pp. 10006-10017 ◽  
Author(s):  
XiaoHui Wang ◽  
Cheng Ji ◽  
HongHan Zhang ◽  
Yu Shan ◽  
YiJie Ren ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Therapeutic Target ◽  
High Throughput Screening ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Potential Therapeutic Target

Nucleus accumbens–associated protein-1 (NAC1) is a transcriptional repressor encoded by the NACC1 gene, which is amplified and overexpressed in various human cancers and plays critical roles in tumor development, progression, and drug resistance. NAC1 has therefore been explored as a potential therapeutic target for managing malignant tumors. However, effective approaches for effective targeting of this nuclear protein remain elusive. In this study, we identified a core unit consisting of Met7 and Leu90 in NAC1's N-terminal domain (amino acids 1–130), which is critical for its homodimerization and stability. Furthermore, using a combination of computational analysis of the NAC1 dimerization interface and high-throughput screening (HTS) for small molecules that inhibit NAC1 homodimerization, we identified a compound (NIC3) that selectively binds to the conserved Leu-90 of NAC1 and prevents its homodimerization, leading to proteasomal NAC1 degradation. Moreover, we demonstrate that NIC3-mediated down-regulation of NAC1 protein sensitizes drug-resistant tumor cells to conventional chemotherapy and enhances the antimetastatic effect of the antiangiogenic agent bevacizumab both in vitro and in vivo. These results suggest that small-molecule inhibitors of NAC1 homodimerization may effectively sensitize cancer cells to some anticancer agents and that NAC1 homodimerization could be further explored as a potential therapeutic target in the development of antineoplastic agents.

Acetylation of PML Plays a Key Role in Histone Deacetylase Inhibitor-Mediated Apoptosis through Enhanced PML Sumoylation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4164-4164
Author(s):  
Fumihiko Hayakawa ◽  
Issay Kitabayashi ◽  
Pier P. Pandolfi ◽  
Tomoki Naoe
Keyword(s):  
Cancer Cells ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Posttranslational Modification ◽  
Hdac Inhibitor ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Antibody Array

Abstract The promyelocytic leukemia (PML) protein is a potent tumor suppressor and proapoptotic factor, and is functionally regulated by posttranslational modification such as phosphorylation, sumoylation, and ubiquitination. Histone deacetylase (HDAC) inhibitors are a promising class of targeted anticancer agents and induce apoptosis to cancer cells. In addition to their effects on histones, HDAC inhibitors increase the acetylation level of several non-histone proteins such as transcription factors, which are important for their effects to cancer cells. However, the mechanism of HDAC inhibitor-induced apoptocis is largely unknown. We report here a novel posttranscriptional modification, acetylation, of PML. By the screening using antibody array, we identified PML as a new acetylation target of Trichostatin A (TSA), a HDAC inhibitor. PML acetylation was enhanced by coexpression of p300 or treatment with TSA. We also showed that increased PML acetylation was associated with increased sumoylation of PML in vitro and in vivo. PML involvement in TSA-induced apoptosis was demonstrated by PML knocking down in Hela cells or PML overexpression in PML−/− MEF cells. Furthermore, PML with acetylation-defective mutation showed disability to mediate the apoptosis, suggesting the importance of PML acetylation for it. Our work provides new insights into the PML regulation by posttranslational modification, and new information about the therapeutic mechanism of HDAC inhibitors.

scholarly journals Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo

2015 ◽  
Vol 6 (9) ◽  
pp. 5269-5283 ◽  
Author(s):  
Jacob Fernández-Gallardo ◽  
Benelita T. Elie ◽  
Tanmoy Sadhukha ◽  
Swayam Prabha ◽  
Mercedes Sanaú ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Renal Cancer ◽  
Anticancer Agents ◽  
Gold Complexes ◽  
First Time

Heterometallic compounds as anticancer agents demonstratingin vivopotential for the first time. Titanocene–gold derivatives: promising candidates for renal cancer.

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