Epigallocatechin gallate-zinc oxide co-crystalline nanoparticles as an anticancer drug that is non-toxic to normal cells

Samutprasert, Pawatsanai; Chiablaem, Khajeelak; Teeraseranee, Chanon; Phaiyarin, Punnawich; Pukfukdee, Puttikorn; Pienpinijtham, Prompong; Svasti, Jisnuson; Palaga, Tanapat; Lirdprapamongkol, Kriengsak; Wanichwecharungruang, Supason

doi:10.1039/c7ra10997k

Cited by 17 publications

(6 citation statements)

References 41 publications

(30 reference statements)

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Section: Resultsmentioning

confidence: 99%

“…67 Co-crystallized zinc oxide with tea polyphenol and epigallocatechin-3-gallate has been shown to induce cell death in PC-3 prostate cancer cells while remaining non-toxic to WI-38 lung fibroblasts. 68 A high concentration of zinc can lead to protein denaturation. 69,70 In response to this, cells undergo a series of adaptive changes to repair the damage.…”

Section: -mentioning

confidence: 99%

See 1 more Smart Citation

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

Chumachenko,

Virych,

Nie

et al. 2023

IJN

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Introduction Cancer chemotherapy faces two major challenges – high toxicity of active substances and tumor resistance to drugs. Low toxic nanocarriers in combination with anticancer agents can significantly increase the effectiveness of therapy. Modern advances in nanotechnology make it easy to create materials with the necessary physical and chemical properties. Methods Two hybrid nanosystems of dextran-polyacrylamide/ zinc oxide nanoparticles (D-PAA/ZnO NPs) were synthesized in aqueous solution with zinc sulphate (D-PAA/ZnO NPs (SO 4 2- )) and zinc acetate (D-PAA/ZnO NPs (-OAc)). The light absorption, fluorescence, dynamic light scattering and transmission electron microscopy for nanocomposite characterization were used. MTT, neutral red uptake and scratch assays were selected as fibroblasts cytotoxicity assays. Cytotoxicity was tested in vitro for normal fibroblasts, MAEC, prostate (LNCaP, PC-3, DU-145) and breast (MDA-MB-231, MCF-7) cancer cells lines. Immunocytochemical methods were used for detection of Ki-67, p53, Bcl-2, Bax, e-cadherin, N-cadherin and CD44 expression. Acridine orange was used to detect morphological changes in cells. Results The radius of ZnO NPs (SO 4 2- ) was 1.5 nm and ZnO NPs (-OAc) was 2 nm. The nanosystems were low-toxic to fibroblasts, MAEC. Cells in the last stages of apoptosis with the formation of apoptotic bodies were detected for all investigated cancer cell lines. Proapoptotic proteins expression in cancer cells indicates an apoptotic death. Increased expression of E-cadherin and N-cadherin was registered for cancer cells line LNCaP, PC-3, DU-145 and MCF-7 after 48 h incubation with D-PAA/ZnO NPs (SO 4 2- ). Conclusion The nanosystems were low-toxic to fibroblasts, MAEC. The D-PAA/ZnO NPs nanosystem synthesized using zinc sulphate demonstrates high cytotoxicity due to destruction of various types of cancer cells in vitro and potentially increases adhesion between cells. Thus, our findings indicate the selective cytotoxicity of D-PAA/ZnO NPs against cancer cells and can be potentially used for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Section: -mentioning

confidence: 99%

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

Chumachenko,

Virych,

Nie

et al. 2023

IJN

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show abstract

“…To do so, we evaluated the cytotoxic effect of each antineoplastic drug, in a range of concentrations from 0.25 to 4 times their IC 50 value for 48 h. Cell viability was assessed using an MTT assay. Drugs that did not cause significant reduction in the viability of MRC-5 cells were considered to have an acceptable toxicological profile and to be non-toxic for normal cells [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

et al. 2022

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Drug combination and drug repurposing are two strategies that allow to find novel oncological therapies, in a faster and more economical process. In our previous studies, we developed a novel model of drug combination using antineoplastic and different repurposed drugs. We demonstrated the combinations of doxorubicin (DOX) + artesunate, DOX + chloroquine, paclitaxel (PTX) + fluoxetine, PTX + fluphenazine, and PTX + benztropine induce significant cytotoxicity in Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Furthermore, it was found that 5-FU + thioridazine and 5-fluorouracil (5-FU) + sertraline can synergistically induce a reduction in the viability of human colorectal adenocarcinoma cell line (HT-29). In this study, we aim to (1) evaluate the biosafety profile of these drug combinations for non-tumoral cells and (2) determine their mechanism of action in cancer cells. To do so, human fetal lung fibroblast cells (MRC-5) fibroblast cells were incubated for 48 h with all drugs, alone and in combination in concentrations of 0.25, 0.5, 1, 2, and 4 times their half-maximal inhibitory concentration (IC50). Cell morphology and viability were evaluated. Next, we designed and constructed a cell microarray to perform immunohistochemistry studies for the evaluation of palmitoyl-protein thioesterase 1 (PPT1), Ki67, cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), and nuclear factor-kappa-B (NF-kB) p65 expression. We demonstrate that these combinations are cytotoxic for cancer cells and safe for non-tumoral cells at lower concentrations. Furthermore, it is also demonstrated that PPT1 may have an important role in the mechanism of action of these combinations, as demonstrated by their ability to decrease PPT1 expression. These results support the use of antimalarial and central nervous system (CNS) drugs in combination regimens with chemotherapeutic agents; nevertheless, additional studies are recommended to further explore their complete mechanisms of action.

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“…Two ionophore molecules can mediate intracellular zinc accumulation by exchanging extracellular Zn 2+ with 2H + [56]. Then, ionophore-zinc complex is taken up by endocytosis, followed by lysosomal disruption to release zinc into the cytoplasm [57].…”

Section: Epigallocatechin Gallate (Egcg)mentioning

confidence: 99%

Role of Zinc and Zinc Ionophores in Brain Health and Depression Especially during the COVID-19 Pandemic

Ahmed¹,

Ghit²,

Houjak³

et al. 2023

COVID-19 Pandemic, Mental Health and Neuroscience - New Scenarios for Understanding and Treatment

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Zinc is a trace metal ion that has a role in both physiological and pathological processes, making it one of the most common and necessary components involved in brain function. Besides, zinc is required for cell proliferation control in a variety of mechanisms, including hormonal regulation of cell division. Also, zinc serves as a biochemical signal to immune cells and transcription factors involved in the synthesis of inflammatory cytokines. On the other hand, zinc has a variety of crucial roles in neurogenesis and also acts as a neuromodulator on a wide range of membrane receptors, ion channels, and transporters. Zinc is produced by neurons under several conditions to activate microglia. The link between zinc dysregulation and psychiatric disorder was that zinc acts as an inhibitory modulator at the N-methyl-D aspartic acid (NMDA) glutamate receptor. Ionophores are ion carrier molecules that reversibly bind and transport ions through biological membranes. Ionophores can be natural or synthetic products. Zinc ionophores such as quercetin, epigallocatechin gallate (EGCG), hinokitol, and proanthocyanidins have been shown to protect brain health, particularly in depression clinically significant depression and depressive symptoms in post-COVID-19 syndrome may have severe implications as it relates to life outcomes quality, herein according to previous research studies, we showed zinc deficiency as a possible risk factor for depression symptoms, which were commonly observed following severe infection of COVID-19.

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Epigallocatechin gallate-zinc oxide co-crystalline nanoparticles as an anticancer drug that is non-toxic to normal cells

Abstract: A tea polyphenol, epigallocatechin-3-gallate (EGCG), can enhance cytotoxicity of Zinc in cancer cells. Here we synthesize hybrid EGCG-ZnO nanoparticles that can kill PC-3 prostate cancer cells at concentrations that are not toxic to normal cells.

Cited by 17 publications

References 41 publications

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

Role of Zinc and Zinc Ionophores in Brain Health and Depression Especially during the COVID-19 Pandemic

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