Neochlorogenic acid anchors MCU-based calcium overload for cancer therapy

2021 ◽  
Author(s):  
Yonglu Li ◽  
Xin Yu ◽  
Lingchi Deng ◽  
Su Zhou ◽  
Yaxuan Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Human Health ◽  
Calcium Overload ◽  
Tetrastigma Hemsleyanum ◽  
Anti Cancer ◽  
Neochlorogenic Acid

Cancer has been threatening human health worldwide, whereas the its clinical therapies remains unsatisfied. In this study, the anti-cancer abilities of Tetrastigma hemsleyanum leaves flavone (TLF) were evaluated in vivo,...

scholarly journals Synthesis and Biological Evaluation of Genistein-IR783 Conjugate: Cancer Cell Targeted Delivery in MCF-7 for Superior Anti-Cancer Therapy

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4120 ◽  
Author(s):  
Yang Guan ◽  
Yi Zhang ◽  
Juan Zou ◽  
Li-Ping Huang ◽  
Mahendra D. Chordia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Natural Product ◽  
Cancer Cell ◽  
Biological Evaluation ◽  
Cyanine Dye ◽  
Therapeutic Window ◽  
Anti Cancer ◽  
Mcf 7

The flavonoid-based natural product genistein is a biologically active compound possessing promising anti-oxidant and anti-cancer properties. Poor pharmacokinetics along with low potency limit however the therapeutic application of genistein in cancer therapy. In order to overcome those limitations and to expand its therapeutic window of efficacy, we sought to covalently attach genistein with a heptamethine cyanine dye—IR 783—for cancer cell targeting and enhanced delivery to tumors. Herein we report the synthesis, a selective detailed characterization and preliminary in vitro/in vivo biological evaluation of genistein-IR 783 conjugate 4. The conjugate 4 displayed improved potency against human breast cancer MCF-7 cells (10.4 ± 1.0 μM) as compared with the parent genistein (24.8 ± 0.5 μM) or IR 783 (25.7 ± 0.7 μM) and exhibited selective high uptake in MCF-7 as against the normal mammary gland MCF-10A cells in various assays. In the cell viability assay, conjugate 4 exhibited over threefold lower potency against MCF-10A cells (32.1 ± 1.1 μM) suggesting that the anti-cancer profile of parent genistein is significantly improved upon conjugation with the dye IR783. Furthermore, the genistein-IR783 conjugate 4 was shown to be especially accumulated in MCF-7 cancer cells by fluorescent intensity measurements and inverted fluorescence microscopy in fixed cells as well as in live cells with time via live cell confocal fluorescence imaging. The mechanism-based uptake inhibition of conjugate 4 was observed with OATPs inhibitor BSP and in part with amiloride, as a macropinocytosis inhibitor. For the first time we have shown amiloride inhibited uptake of cyanine dye by about ~40%. Finally, genistein-IR 783 conjugate 4 was shown to be localized in MCF-7 tumor xenografts of mice breast cancer model via in vivo near infrared fluorescence (NIRF) imaging. In conclusion, conjugation of genistein with cyanine dye IR783 indeed improved its pharmacological profile by cancer cell selective uptake and targeting and therefore warrants further investigations as a new anti-cancer therapeutics derived from natural product genistein.

scholarly journals New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1523 ◽  
Author(s):  
Yuanyuan Fu ◽  
Qianqian Gu ◽  
Li Luo ◽  
Jiecheng Xu ◽  
Yuping Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Screening Method ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Single Target ◽  
Anti Cancer

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

Y2O3:Yb,Er@mSiO2–CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging

Nanoscale ◽  
2015 ◽  
Vol 7 (28) ◽  
pp. 12180-12191 ◽  
Author(s):  
Dan Yang ◽  
Guixin Yang ◽  
Xingmei Wang ◽  
Ruichan Lv ◽  
Shili Gai ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Fluorescence Imaging ◽  
Hollow Spheres ◽  
Anti Cancer ◽  
Imaging Properties

Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) exhibit high anti-cancer efficacy due to enabling synergistic therapy and their excellent in vitro and in vivo CT and up-conversion fluorescence imaging properties.

Controllable silicon nanostructures featuring stable fluorescence and intrinsic in vitro and in vivo anti-cancer activity

2019 ◽  
Vol 7 (40) ◽  
pp. 6247-6256
Author(s):  
Binbin Chu ◽  
Sicong Wu ◽  
Xiaoyuan Ji ◽  
Runzhi Chen ◽  
Bin Song ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Silicon Nanostructures ◽  
Synthetic Approach ◽  
Microwave Assisted ◽  
Anti Cancer ◽  
Si Nanostructures ◽  
Cancer Activity

A facile microwave-assisted synthetic approach enables the fabrication of different-dimensional Si nanostructures with unique optical merits for cancer therapy.

scholarly journals Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria D. Turubanova ◽  
Tatiana A. Mishchenko ◽  
Irina V. Balalaeva ◽  
Iuliia Efimova ◽  
Nina N. Peskova ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Adaptive Immune System ◽  
Immunogenic Cell Death ◽  
Immunodeficient Mice ◽  
Anti Cancer ◽  
Molecular Patterns

AbstractThe immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2 (λex 615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.

scholarly journals Metformin alters signaling induced crosstalk and homeostasis in the carcinogenesis paradigm “Epistemology of the origin of cancer”

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 12
Author(s):  
Björn L.D.M. Brücher ◽  
Ijaz S. Jamall
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Significant Proportion ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Beneficial Effects ◽  
Anti Cancer ◽  
Anti Inflammatory

The anti-hyperglycemic drug, Metformin, is effective in treating early stages of diabetes and has been associated with a 37% decrease in cancer incidence. While the precise mechanisms for the anti-cancer effects of Metformin remain to be elucidated, this review shows the multiplicity of its effects on interdicting signaling and crosstalk, anti-inflammatory effects and in restoring homeostasis, which, taken together, go beyond its well-known anti-hyperglycemic effect that serves as the basis for its use in type 2 diabetes. Metformin is much more than a one-trick pony. The recent discovery of several signaling pathways influenced by Metformin appears to have potential value in cancer therapy. Based on what we know at present, Metformin promotes beneficial effects attributed to its anti-inflammatory and anti-fibrotic effects largely demonstrated in vitro. Metformin activates or upregulates while it simultaneously inhibits or downregulates multiple signaling pathways of cell-cycle arrest and apoptosis accompanied by oxidative stress, which are in accordance with the 6-step sequence of carcinogenesis. Furthermore, in vivo studies in laboratory animals and in cancer patients are beginning to address the magnitude of the anti-cancer effects and delineate its anti-cancer effects. In this context, results from prior pancreatic and non-pancreatic cancer trials, which contained a significant proportion of the patient population treated with Metformin, will have to be reexamined in light of the observed anti-cancerous effects to gain additional insights. The detailed exploration of Metformin in the context of the “Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer” can provide helpful insights into the anti-proliferative mechanisms and could play a relevant role in anti-cancer therapy in the future.

Gene of the month: PIK3CA

2015 ◽  
Vol 68 (4) ◽  
pp. 253-257 ◽  
Author(s):  
K Lai ◽  
M C Killingsworth ◽  
C S Lee
Keyword(s):  
Cancer Therapy ◽  
In Vivo Model ◽  
Phosphatidylinositol 3 Kinase ◽  
Cellular Functions ◽  
Combined Use ◽  
Wide Range ◽  
Anti Cancer ◽  
Attractive Therapeutic Target ◽  
Induced Apoptosis

PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K) which through its role in the PI3K/Akt pathway is important for the regulation of important cellular functions such as proliferation, metabolism and protein synthesis, angiogenesis and apoptosis. Mutations in PIK3CA are known to be involved in a wide range of human cancers and mutant PIK3CA is thought to act as an oncogene. The specific PIK3CA inhibitor, NVP-BYL719, has displayed promising results in cancer therapy and is currently under clinical trials. Furthermore, PI3K regulates autophagy, a cellular process that recycles proteins and organelles through lysosomal degradation and has recently been recognised as an attractive therapeutic target due to its pro- and anti-cancer properties. Several studies have attempted to investigate the effects of combining the inhibition of both PI3K and autophagy in cancer therapy, and an in vivo model has demonstrated that the combined use of a concomitant PI3K and autophagy inhibitor induced apoptosis in glioma cells.

Flavonoid-Based Cancer Therapy: An Updated Review

2020 ◽  
Vol 20 (12) ◽  
pp. 1398-1414 ◽  
Author(s):  
Elham Hosseinzadeh ◽  
Ali Hassanzadeh ◽  
Faroogh Marofi ◽  
Mohammad Reza Alivand ◽  
Saeed Solali
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Anti Cancer ◽  
Phytochemical Compounds ◽  
Proliferation And Metastasis ◽  
The Relationship

: As cancers are one of the most important causes of human morbidity and mortality worldwide, researchers try to discover novel compounds and therapeutic approaches to decrease survival of cancer cells, angiogenesis, proliferation and metastasis. In the last decade, use of special phytochemical compounds and flavonoids was reported to be an interesting and hopeful tactic in the field of cancer therapy. Flavonoids are natural polyphenols found in plant, fruits, vegetables, teas and medicinal herbs. Based on reports, over 10,000 flavonoids have been detected and categorized into several subclasses, including flavonols, anthocyanins, flavanones, flavones, isoflavones and chalcones. It seems that the anticancer effect of flavonoids is mainly due to their antioxidant and anti inflammatory activities and their potential to modulate molecular targets and signaling pathways involved in cell survival, proliferation, differentiation, migration, angiogenesis and hormone activities. The main aim of this review is to evaluate the relationship between flavonoids consumption and cancer risk, and discuss the anti-cancer effects of these natural compounds in human cancer cells. Hence, we tried to collect and revise important recent in vivo and in vitro researches about the most effective flavonoids and their main mechanisms of action in various types of cancer cells.

Size and surface controllable metal–organic frameworks (MOFs) for fluorescence imaging and cancer therapy

Nanoscale ◽  
2018 ◽  
Vol 10 (13) ◽  
pp. 6205-6211 ◽  
Author(s):  
Xuechuan Gao ◽  
Ruixue Cui ◽  
Guanfeng Ji ◽  
Zhiliang Liu
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Fluorescence Imaging ◽  
Metal Organic Framework ◽  
Metal Organic Frameworks ◽  
Anti Cancer ◽  
Metal Organic ◽  
Organic Framework

This work presents a novel size and surface controllable metal–organic framework, UIO-66-NH2-FA-5-FAM/5-FU, which possesses the superior characteristics of targeted identification of cancer cells, bioimaging and obvious anti-cancer effects in vivo.

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