scholarly journals Small Molecule Binds with Lymphocyte Antigen 6K to Induce Cancer Cell Death

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 509 ◽  
Author(s):  
Senyi Benti ◽  
Purushottam B. Tiwari ◽  
Dustin W. Goodlett ◽  
Leily Daneshian ◽  
Grant B. Kern ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Breast Cancers ◽  
Cancer Cell Growth ◽  
Lymphocyte Antigen ◽  
Pharmacological Inhibition ◽  
Cancer Cell Death ◽  
Small Molecule Libraries

Elevated gene expression of Lymphocyte antigen 6K (LY6K) in cancer cells is associated with poor survival outcomes in multiple different cancer types including cervical, breast, ovarian, lung, and head and neck cancer. Since inhibition of LY6K expression inhibits cancer cell growth, we set out to explore whether pharmacological inhibition of LY6K could produce the same effect. We screened small molecule libraries for direct binding to recombinant LY6K protein in a surface plasmon resonance assay. We found that NSC243928 directly binds to the full-length and mature forms of LY6K and inhibits growth of HeLa cells that express LY6K. NSC243928 did not display binding with LY6D or LY6E. Our data demonstrate a first-time proof of principle study that pharmacological inhibition of LY6K using small molecules in cancer cells is a valid approach to developing targeted therapies against LY6K. This approach will be specifically relevant in hard-to-treat cancers where LY6K is highly expressed, such as cervical, pancreatic, ovarian, head and neck, lung, gastric, and triple-negative breast cancers.

scholarly journals Effect of S14161 Small Molecule and Glaucium Flavum Extract on A549 Cancer Cells

2021 ◽  
Vol 10 ◽  
pp. e2151
Author(s):  
Mahshad Kalantari ◽  
Maliheh Entezari ◽  
Milad Ashrafizadeh ◽  
Abolfazl Movafagh ◽  
Kiavash Hushmandi
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Lethal Effect ◽  
Herbal Remedies ◽  
Drug Candidates ◽  
Cancer Cell Death ◽  
Common Cancer

Background: Lung cancer is the fifth most common cancer in Iran. Due to the side effects of common cancer treatments, everyone has turned to herbal remedies and new treatments. This study aimed to compare the effect of S14161 small molecule and Glaucium flavum extract on the induction of apoptosis in A549 cancer cells. Materials and Methods: In this experimental study, the A549 cell line was treated with different concentrations of G. flavum and S14161 on days 1, 3, and 5. Also, half maximal inhibitory concentrations (IC 50) for both G. flavum and S14161 were measured. In addition, the quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to investigate the effects of S14161 and G. flavum extract on the expressions level of Bax, Bad, P53, and Bcl2 genes. Results: Results showed that both the combination of S14161 and G. flavum extract resulted in cell death and reduced cancer cell viability. Nevertheless, the viability rate was greater by S14161, and this small molecule significantly increased the expression of Bax, P53, and Bad apoptotic genes and decreased the expression of the Bcl2 gene, which shows the induced apoptotic death and lethal effect of S14161 in comparison with G. flavum extract. Conclusion: Our study showed that S14161 had fewer IC50 and caused cell death by inhibiting the PI3K/AKT pathway, and G. flavum caused cancer cell death due to its alkaloid compounds. Therefore, both compounds are recommended as drug candidates for the treatment of lung cancer.

scholarly journals A small molecule targeting glutathione activates Nrf2 and inhibits cancer cell growth through promoting Keap-1S-glutathionylation and inducing apoptosis

RSC Advances ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. 792-804 ◽  
Author(s):  
LiHong Wang ◽  
GuoJing Qu ◽  
YuanDi Gao ◽  
Le Su ◽  
Qing Ye ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Cancer Cell Growth

The level of glutathione (GSH) is increased in many cancer cells.

Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

2021 ◽  
Author(s):  
Wooram Park ◽  
Seok-Jo Kim ◽  
Paul Cheresh ◽  
Jeanho Yun ◽  
Byeongdu Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cancer Cell ◽  
High Sensitivity ◽  
Intrinsic Pathway ◽  
Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

scholarly journals Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3610
Author(s):  
Valeria De Matteis ◽  
Mariafrancesca Cascione ◽  
Loris Rizzello ◽  
Daniela Erminia Manno ◽  
Claudia Di Guglielmo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Calcium Release ◽  
Chemical Properties ◽  
Chemical Route ◽  
Au Nps ◽  
Anticancer Properties ◽  
Cancer Cell Death ◽  
Combined Strategy

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment.

scholarly journals Mitochondrial Transfer in Cancer: A Comprehensive Review

2021 ◽  
Vol 22 (6) ◽  
pp. 3245
Author(s):  
Luca X. Zampieri ◽  
Catarina Silva-Almeida ◽  
Justin D. Rondeau ◽  
Pierre Sonveaux
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Current Knowledge ◽  
Cancer Cell Proliferation ◽  
Tunneling Nanotubes ◽  
Comprehensive Review ◽  
Cancer Cell Death ◽  
Mitochondrial Transfer ◽  
Metabolic Activities

Depending on their tissue of origin, genetic and epigenetic marks and microenvironmental influences, cancer cells cover a broad range of metabolic activities that fluctuate over time and space. At the core of most metabolic pathways, mitochondria are essential organelles that participate in energy and biomass production, act as metabolic sensors, control cancer cell death, and initiate signaling pathways related to cancer cell migration, invasion, metastasis and resistance to treatments. While some mitochondrial modifications provide aggressive advantages to cancer cells, others are detrimental. This comprehensive review summarizes the current knowledge about mitochondrial transfers that can occur between cancer and nonmalignant cells. Among different mechanisms comprising gap junctions and cell-cell fusion, tunneling nanotubes are increasingly recognized as a main intercellular platform for unidirectional and bidirectional mitochondrial exchanges. Understanding their structure and functionality is an important task expected to generate new anticancer approaches aimed at interfering with gains of functions (e.g., cancer cell proliferation, migration, invasion, metastasis and chemoresistance) or damaged mitochondria elimination associated with mitochondrial transfer.

scholarly journals KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics

2018 ◽  
Vol 115 (20) ◽  
pp. E4613-E4622 ◽  
Author(s):  
Bojan Milic ◽  
Anirban Chakraborty ◽  
Kyuho Han ◽  
Michael C. Bassik ◽  
Steven M. Block
Keyword(s):  
Cancer Cell ◽  
Small Molecule ◽  
Single Molecule ◽  
Small Molecule Inhibitors ◽  
Cancer Cell Growth ◽  
Combination Drug ◽  
Cancer Chemotherapeutics ◽  
Development Of Resistance ◽  
Molecule Inhibitor ◽  
Mechanochemical Cycle

Eg5, a mitotic kinesin, has been a target for anticancer drug development. Clinical trials of small-molecule inhibitors of Eg5 have been stymied by the development of resistance, attributable to mitotic rescue by a different endogenous kinesin, KIF15. Compared with Eg5, relatively little is known about the properties of the KIF15 motor. Here, we employed single-molecule optical-trapping techniques to define the KIF15 mechanochemical cycle. We also studied the inhibitory effects of KIF15-IN-1, an uncharacterized, commercially available, small-molecule inhibitor, on KIF15 motility. To explore the complementary behaviors of KIF15 and Eg5, we also scored the effects of small-molecule inhibitors on admixtures of both motors, using both a microtubule (MT)-gliding assay and an assay for cancer cell viability. We found that (i) KIF15 motility differs significantly from Eg5; (ii) KIF15-IN-1 is a potent inhibitor of KIF15 motility; (iii) MT gliding powered by KIF15 and Eg5 only ceases when both motors are inhibited; and (iv) pairing KIF15-IN-1 with Eg5 inhibitors synergistically reduces cancer cell growth. Taken together, our results lend support to the notion that a combination drug therapy employing both inhibitors may be a viable strategy for overcoming chemotherapeutic resistance.

Cancer-associated fibroblasts (CAFs) in thyroid papillary carcinoma: molecular networks and interactions

2021 ◽  
pp. jclinpath-2020-207357
Author(s):  
Jeehoon Ham ◽  
Bin Wang ◽  
Joseph William Po ◽  
Amandeep Singh ◽  
Navin Niles ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Molecular Networks ◽  
Cancer Cell Growth ◽  
Molecular Events

In 1989, Stephen Paget proposed the ‘seed and soil’ theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.

Fibrin and Cancer Cell Growth: Problems in the Evaluation of Experimental Models

1979 ◽  
Author(s):  
Andreina Poggi
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Primary Tumour ◽  
Antiplatelet Agent ◽  
Experimental Models ◽  
Surgical Removal ◽  
Antiinflammatory Drugs ◽  
Cancer Cell Growth ◽  
Lung Carcinoma Cells

Studies on the role of fibrin in experimental cancer growth should take into account the following problems: 1) during growth and dissemination of experimental tumours, haemostatic changes may occur which vary depending on the route of inoculation of cancer cells and on the tissue wherethe tumour grows. Thrombocytopenia, haemolytic microangiopathic anaemia and decreased survival of fibrinogen were observed during spontaneous dissemination to the lung of i.m. implanted Lewis Lung Carcinoma cells, not when metastatic growth occurred after surgical removal of the primary tumour or lung nodules developed following i.v. injection of the same cells. 2) Treatment of experimental tumours with drugs active on the haemostatic system may have different effects depending on the stage of growth of the tumour. This observation (which we have made with both warfarin and a defibrinating enzyme in murine metastasizing tumours) could suggest that fibrin may play different roles at different phases of cancer cell growth. 3) The supposed antiturooral activity of drugs active on the haemostatic system may be also influenced by other factors, such as a direct activity on cancer cells or on the host’s immune system or on blood supply to the tumour. As an example, non steroidal antiinflammatory drugs may act not only as antiplatelet agent but also as inhibitors of prostaglandin synthesis by cancer cells and some snake venoms may influence cancer cell growth not only through defibrination, but also with their iinnu-nodepressant properties. (Supported by Italian CNR and NIM. MCI, USA).

Rational design of water-dispersible and biocompatible nanoprobes with H2S-triggered NIR emission for cancer cell imaging

2020 ◽  
Vol 8 (28) ◽  
pp. 6013-6016
Author(s):  
Hengyan Liu ◽  
Ge Xu ◽  
Tianli Zhu ◽  
Rongchen Wang ◽  
Jiahui Tan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Small Molecule ◽  
Rational Design ◽  
Cell Imaging ◽  
Imaging Modality ◽  
Aqueous Solubility ◽  
Water Dispersible ◽  
Nir Emission ◽  
Small Molecule Probe

A nanoprobe with good aqueous solubility and biocompatibility by trapping an H2S-activatable small molecule probe in the interior of surface cross-linked micelles was fabricated for imaging of H2S-rich cancer cells in a dual-color imaging modality.

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