scholarly journals Natural Products as Inducers of Non-Canonical Cell Death: A Weapon against Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 304
Author(s):  
Giulia Greco ◽  
Elena Catanzaro ◽  
Carmela Fimognari
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Antitumor Agents ◽  
Apoptotic Cell ◽  
Antitumor Effects ◽  
Full Characterization ◽  
Toxicological Profile ◽  
Long Time ◽  
Synthetic Derivatives

Apoptosis has been considered the main mechanism induced by cancer chemotherapeutic drugs for a long time. This paradigm is currently evolving and changing, as increasing evidence pointed out that antitumor agents could trigger various non-canonical or non-apoptotic cell death types. A considerable number of antitumor drugs derive from natural sources, both in their naturally occurring form or as synthetic derivatives. Therefore, it is not surprising that several natural compounds have been explored for their ability to induce non-canonical cell death. The aim of this review is to highlight the potential antitumor effects of natural products as ferroptosis, necroptosis, or pyroptosis inducers. Natural products have proven to be promising non-canonical cell death inducers, capable of overcoming cancer cells resistance to apoptosis. However, as discussed in this review, they often lack a full characterization of their antitumor activity together with an in-depth investigation of their toxicological profile.

A Thorough Theoretical Exploration of Intriguing Characteristics of Cyclo[18]carbon: Geometry, Bonding Nature, Aromaticity, Weak Interaction, Reactivity, Excited States, Vibrations, Molecular Dynamics and Various Molecular Properties

2019 ◽  
Author(s):  
Tian Lu ◽  
Qinxue Chen ◽  
Zeyu Liu
Keyword(s):  
Molecular Dynamics ◽  
Excited States ◽  
Electronic Excitation ◽  
Ring Structure ◽  
Molecular Properties ◽  
Molecular Vibration ◽  
Full Characterization ◽  
Long Time ◽  
Almost All

Although cyclo[18]carbon has been theoretically and experimentally investigated since long time ago, only very recently it was prepared and directly observed by means of STM/AFM in condensed phase (Kaiser et al., <i>Science</i>, <b>365</b>, 1299 (2019)). The unique ring structure and dual 18-center π delocalization feature bring a variety of unusual characteristics and properties to the cyclo[18]carbon, which are quite worth to be explored. In this work, we present an extremely comprehensive and detailed investigation on almost all aspects of the cyclo[18]carbon, including (1) Geometric characteristics (2) Bonding nature (3) Electron delocalization and aromaticity (4) Intermolecular interaction (5) Reactivity (6) Electronic excitation and UV/Vis spectrum (7) Molecular vibration and IR/Raman spectrum (8) Molecular dynamics (9) Response to external field (10) Electron ionization, affinity and accompanied process (11) Various molecular properties. We believe that our full characterization of the cyclo[18]carbon will greatly deepen researchers' understanding of this system, and thereby help them to utilize it in practice and design its various valuable derivatives.

A Thorough Theoretical Exploration of Intriguing Characteristics of Cyclo[18]carbon: Geometry, Bonding Nature, Aromaticity, Weak Interaction, Reactivity, Excited States, Vibrations, Molecular Dynamics and Various Molecular Properties

2019 ◽  
Author(s):  
Tian Lu ◽  
Qinxue Chen ◽  
Zeyu Liu
Keyword(s):  
Molecular Dynamics ◽  
Excited States ◽  
Electronic Excitation ◽  
Ring Structure ◽  
Molecular Properties ◽  
Molecular Vibration ◽  
Full Characterization ◽  
Long Time ◽  
Almost All

Although cyclo[18]carbon has been theoretically and experimentally investigated since long time ago, only very recently it was prepared and directly observed by means of STM/AFM in condensed phase (Kaiser et al., <i>Science</i>, <b>365</b>, 1299 (2019)). The unique ring structure and dual 18-center π delocalization feature bring a variety of unusual characteristics and properties to the cyclo[18]carbon, which are quite worth to be explored. In this work, we present an extremely comprehensive and detailed investigation on almost all aspects of the cyclo[18]carbon, including (1) Geometric characteristics (2) Bonding nature (3) Electron delocalization and aromaticity (4) Intermolecular interaction (5) Reactivity (6) Electronic excitation and UV/Vis spectrum (7) Molecular vibration and IR/Raman spectrum (8) Molecular dynamics (9) Response to external field (10) Electron ionization, affinity and accompanied process (11) Various molecular properties. We believe that our full characterization of the cyclo[18]carbon will greatly deepen researchers' understanding of this system, and thereby help them to utilize it in practice and design its various valuable derivatives.

scholarly journals Combinatorial Effect of Magnetic Field and Radiotherapy in PDAC Organoids: A Pilot Study

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 609
Author(s):  
Luca Nicosia ◽  
Filippo Alongi ◽  
Silvia Andreani ◽  
Ruggero Ruggieri ◽  
Borislav Rusev ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Treatment Plan ◽  
Anatomical Variations ◽  
Ductal Adenocarcinoma ◽  
Treatment Technique ◽  
Contrast Resolution ◽  
Long Time ◽  
Almost All

Pancreatic ductal adenocarcinoma (PDAC) is highly refractory to systemic treatment, including radiotherapy (RT) either as alone or in combination with chemotherapy. Magnetic resonance (MR)-guided RT is a novel treatment technique which conjugates the high MR imaging contrast resolution to the possibility of re-adapting treatment plan to daily anatomical variations. Magnetic field (MF) might exert a biological effect that could be exploited to enhance radiation effect. The aim of the present study was to lay the preclinical basis of the MF effect by exploring how it modifies the response to radiation in organoid cultures established from PDAC. The short-term effect of radiation, alone or in combination with MF, was evaluated in patient-derived organoids (PDOs) and monolayer cell cultures. Cell viability, apoptotic cell death, and organoid size following exposure to the treatment were evaluated. PDOs demonstrated limited sensitivity at clinically relevant doses of radiation. The combination of radiation and MF demonstrated superior efficacy than monotherapy in almost all the PDOs tested. PDOs treated with combination of radiation and MF were significantly smaller in size and some showed increased cell death as compared to the monotherapy with radiation. Long-time exposure to 1.5T MF can increase the therapeutic efficacy of radiation in PDAC organoids.

scholarly journals Characterization of Stanniocalcin 2, a Novel Target of the Mammalian Unfolded Protein Response with Cytoprotective Properties

2004 ◽  
Vol 24 (21) ◽  
pp. 9456-9469 ◽  
Author(s):  
Daisuke Ito ◽  
John R. Walker ◽  
Charlie S. Thompson ◽  
Isabella Moroz ◽  
William Lin ◽  
...  
Keyword(s):  
Cell Death ◽  
Unfolded Protein Response ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
In Vivo Studies ◽  
Unfolded Protein ◽  
Stanniocalcin 2 ◽  
Novel Target ◽  
Protein Response

ABSTRACT Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces a highly conserved homeostatic response in all eukaryotic cells, termed the unfolded-protein response (UPR). Here we describe the characterization of stanniocalcin 2 (STC2), a mammalian homologue of a calcium- and phosphate-regulating hormone first identified in fish, as a novel target of the UPR. Expression of STC2 gene is rapidly upregulated in cultured cells after exposure to tunicamycin and thapsigargin, by ATF4 after activation of the ER-resident kinase PERK. In addition, STC2 expression is also activated in neuronal cells by oxidative stress and hypoxia but not by several cellular stresses unrelated to the UPR. In contrast, expression of another homologue, STC1, is only upregulated by hypoxia independent of PERK or ATF4 expression. In vivo studies revealed that rat cortical neurons rapidly upregulate STC2 after transient middle cerebral artery occlusion. Finally, siRNA-mediated inhibition of STC2 expression renders N2a neuroblastoma cells and HeLa cells significantly more vulnerable to apoptotic cell death after treatment with thapsigargin, and overexpression of STC2 attenuated thapsigargin-induced cell death. Consequently, induced STC2 expression is an essential feature of survival component of the UPR.

Demethylzeylasteral Exerts Antitumor Effects via Disruptive Autophagic Flux and Apoptotic Cell Death in Human Colorectal Cancer Cells and Increases Cell Chemosensitivity to 5-Fluorouracil

2021 ◽  
Vol 21 ◽  
Author(s):  
Guiyuan Liu ◽  
Dengxiang Lai ◽  
Yi Jiang ◽  
Hongjing Yang ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autophagic Flux ◽  
Human Colorectal Cancer ◽  
Antitumor Effects ◽  
Tripterygium Wilfordii Hook F ◽  
Pharmacologically Active

Background: Demethylzeylasteral (ZST93), a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF), has been reported to exert antineoplastic effects in several cancer cell types. However, the anti-tumour effects of ZST93 in human colorectal cancer (CRC) cells are unknown. Objective: The aim of the present study was to evaluate the antitumor effects of ZST93 on cell cycle arrest, disruptive autophagic flux, apoptotic cell death, and enhanced chemosensitivity to 5-FU in humans CRC cells. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) assay, colony formation assay, flow cytometry, immunoblotting, immunofluorescence, 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, and autophagy analysis were used to evaluate the effects of ZST93 on cell viability, cell cycle progression, apoptosis and autophagy in two human CRC cell lines. Moreover, ZST93’s combined anti-tumour effects with 5-fluorouracil (5-FU) were evaluated. Results: ZST93 inhibited CRC cell proliferation and growth. It was responsible for blocked cell cycle transition by arresting CRC cells in the G0/G1 phase via down-regulation of CDK4, CDK6, Cyclin D1, and c-MYC. Moreover, ZST93 induced suppressive autophagic flux and caspase-3-dependent cell death, which were further strengthened by the blocking of the autophagy process using chloroquine (CQ). Moreover, ZST93 enhanced CRC cells’ chemosensitivity to 5-FU via modulation of autophagy and apoptosis. Conclusion: ZST93 exerts anti-tumour effects via disruptive autophagic flux and apoptotic cell death in human CRC cells and increases cell chemosensitivity to 5-FU. These results provide insights into the utilisation of ZST93 as an adjuvant or direct autophagy inhibitor and suggest ZST93 as a novel therapeutic strategy for treating CRC.

scholarly journals Characterization of Cyclin E Expression in Multiple Myeloma and Its Functional Role in Seliciclib-Induced Apoptotic Cell Death

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e33856 ◽  
Author(s):  
Liat Josefsberg Ben-Yehoshua ◽  
Katia Beider ◽  
Avichai Shimoni ◽  
Olga Ostrovsky ◽  
Michal Samookh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Functional Role ◽  
Apoptotic Cell ◽  
Cyclin E ◽  
Apoptotic Cell Death

scholarly journals Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Ning Wang ◽  
Yibin Feng
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Cell Fate ◽  
Mammalian Cells ◽  
Apoptotic Cell ◽  
Rapid Expansion ◽  
Drug Study

Autophagy is a homeostatic process that is highly conserved across different types of mammalian cells. Autophagy is able to relieve tumor cell from nutrient and oxidative stress during the rapid expansion of cancer. Excessive and sustained autophagy may lead to cell death and tumor shrinkage. It was shown in literature that many anticancer natural compounds and extracts could initiate autophagy in tumor cells. As summarized in this review, the tumor suppressive action of natural products-induced autophagy may lead to cell senescence, provoke apoptosis-independent cell death, and complement apoptotic cell death by robust or target-specific mechanisms. In some cases, natural products-induced autophagy could protect tumor cells from apoptotic death. Technical variations in detecting autophagy affect data quality, and study focus should be made on elaborating the role of autophagy in deciding cell fate. In vivo study monitoring of autophagy in cancer treatment is expected to be the future direction. The clinical-relevant action of autophagy-inducing natural products should be highlighted in future study. As natural products are an important resource in discovery of lead compound of anticancer drug, study on the role of autophagy in tumor suppressive effect of natural products continues to be necessary and emerging.

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