A supramolecular adduct of tegafur and syringic acid: the first tegafur-nutraceutical cocrystal with perfected in vitro and in vivo characteristics as well as synergized anticancer activities

2020 ◽  
Vol 44 (37) ◽  
pp. 15994-16005
Author(s):  
Yue-Ming Yu ◽  
Ming-Chao Yu ◽  
Ling-Yang Wang ◽  
Yan-Tuan Li ◽  
Zhi-Yong Wu ◽  
...  
Keyword(s):  
Syringic Acid ◽  
Anticancer Activities ◽  
Antitumor Activities ◽  
Supramolecular Adduct

The in vitro and in vivo properties as well as synergistic antitumor activities of the first tegafur-nutraceutical cocrystal are reported.

Synthesis and biological evaluation of thiophene-based hydroxamate derivatives as HDACis with antitumor activities

2020 ◽  
Vol 12 (8) ◽  
pp. 655-672 ◽  
Author(s):  
Feifei Yang ◽  
Lina Han ◽  
Na Zhao ◽  
Yang Yang ◽  
Di Ge ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Xenograft Model ◽  
Biological Evaluation ◽  
Anticancer Activities ◽  
Antitumor Activities ◽  
Cancer Treatments

Aim:   Histone deacetylases (HDACs) are one of the validated targets for cancer treatments. In our previous work, we designed a series of bis-substituted aromatic amide HDAC inhibitors (HDACis), among which compounds 7 and 8 showed promising anticancer effects. However, the low solubilities prevented their subsequent developments. We developed additional thiophene-based hydroxamate HDACis in order to improve their physicochemical properties. Materials & methods: In vitro biological evaluations of these analogs revealed potent antiproliferative and antimigrated activities. More importantly, compound 10h exhibited excellent in vivo antitumor activities in MDA-MB-231 xenograft model mice. Furthermore, 10h showed better anticancer activities and drug-like properties than 7. Results & conclusion: Our results proved that thiophene-based hydroxamate HDACis can serve as a promising framework for developing potential anticancer agents.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

scholarly journals Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 498
Author(s):  
Mariaevelina Alfieri ◽  
Antonietta Leone ◽  
Alfredo Ambrosone
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Plant Biotechnology ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Long Distance ◽  
In Vivo Models ◽  
Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

scholarly journals STRUCTURE-BASED MULTITARGETED MOLECULAR DOCKING ANALYSIS OF PYRAZOLE-CONDENSED HETEROCYCLICS AGAINST LUNG CANCER

2021 ◽  
pp. 157-169
Author(s):  
JAINEY P. JAMES ◽  
AISWARYA T. C. ◽  
SNEH PRIYA ◽  
DIVYA JYOTHI ◽  
SHESHAGIRI R. DIXIT
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Mode ◽  
Pharmacophore Modeling ◽  
In Vivo Studies ◽  
Spectral Studies ◽  
Pyrazole Derivatives ◽  
Anticancer Activities

Objective: The significant drawbacks of chemotherapy are that it destroys healthy cells, resulting in adverse effects. Hence, there is a need to adopt new techniques to develop cancer-specific chemicals that target the molecular pathways in a non-toxic fashion. This study aims to screen pyrazole-condensed heterocyclics for their anticancer activities and analyse their enzyme inhibitory potentials EGFR, ALK, VEGFR and TNKS receptors. Methods: The structures of the compounds were confirmed by IR, NMR and Mass spectral studies. The in silico techniques applied in this study were molecular docking and pharmacophore modeling to analyse the protein-ligand interactions, as they have a significant role in drug discovery. Drug-likeness properties were assessed by the Lipinski rule of five and ADMET properties. Anticancer activity was performed by in vitro MTT assay on lung cancer cell lines. Results: The results confirm that all the synthesised pyrazole derivatives interacted well with the selected targets showing docking scores above-5 kcal/mol. Pyrazole 2e interacted well with all the four lung cancer targets with its stable binding mode and was found to be potent as per the in vitro reports, followed by compounds 3d and 2d. Pharmacophore modeling exposed the responsible features responsible for the anticancer action. ADMET properties reported that all the compounds were found to have properties within the standard limit. The activity spectra of the pyrazoles predicted that pyrazolopyridines (2a-2e) are more effective against specific receptors such as EGFR, ALK and Tankyrase. Conclusion: Thus, this study suggests that the synthesised pyrazole derivatives can be further investigated to validate their enzyme inhibitory potentials by in vivo studies.

scholarly journals Pladienolides, New Substances from Culture of Streptomyces platensis Mer-11107 III. In Vitro and In Vivo Antitumor Activities

2004 ◽  
Vol 57 (3) ◽  
pp. 188-196 ◽  
Author(s):  
YOSHIHARU MIZUI ◽  
TAKASHI SAKAI ◽  
MASAO IWATA ◽  
TOSHIMITSU UENAKA ◽  
KIYOSHI OKAMOTO ◽  
...  
Keyword(s):  
Antitumor Activities ◽  
Streptomyces Platensis

Novel Mitochondrial Targeting Multifunctional Surface Charge-Reversal Polymeric Nanoparticles for Cancer Treatment

2019 ◽  
Vol 15 (11) ◽  
pp. 2151-2163 ◽  
Author(s):  
Lei Fang ◽  
Huaying Fan ◽  
Chunjing Guo ◽  
Linhan Cui ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Polymeric Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
Hydrodynamic Diameter ◽  
Mitochondrial Targeting ◽  
Anticancer Activities ◽  
Charge Reversal

Polymeric nanoparticles were widely used as delivery vehicles for targeted delivery of anticancer drugs, because of their targeting property and versatility. Mitochondria are one of the important organelles that regulate the apoptosis of cancer cells and can be considered as a pivotal target for cancer treatment. A pH-responsive charge-reversal and mitochondrial targeting nanoparticles, Vitamin B6-oligomeric hyaluronic acid-dithiodipropionic acid-berberine (B6-oHA-SS-Ber), were prepared in this study. Ber is a lipophilic cation that was conjugated with oHA through disulfide bonds to produce mitochondria-targeted conjugates (oHA-SS-Ber). B6 was conjugated to oHA to obtain B6-oHA-SS-Ber and the two types of Cur-loaded nanoparticles (Cur-NPs) were formulated by the dialysis method. Due to pKa of B6, the charge they carried in the tumor tissue acidic microenvironment can be transferred from negative charge to positive charge, further targeting mitochondria. In our study, we successfully synthesized B6-HA-SS-Ber and characterized the structure by 1H-NMR. According to the results of transmission electron microscopy (TEM), we found that the B6-oHA-SS-Ber/Cur micelles could self-assembled in water to form spherical nanoparticles, with a hydrodynamic diameter of 172.9±13 nm. Moreover, in vitro cytotoxicity, cellular uptake, lysosome escape and mitochondrial distribution researches revealed the better effect of B6-oHA-SS-Ber/Cur micelles in comparison to oHA-SS-Ber/Cur. In vivo anticancer activities indicated that the B6-oHA-SS-Ber/Cur micelles exhibited effective inhibition of tumor growth.

Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells

2020 ◽  
Vol 52 (4) ◽  
pp. 401-410
Author(s):  
Mengyu Xi ◽  
Wan He ◽  
Bo Li ◽  
Jinfeng Zhou ◽  
Zhijian Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Anticancer Activities ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common category and disease entity of non-Hodgkin lymphoma. Osalmide and pterostilbene are natural products with anticancer activities via different mechanism. In this study, using a new synthetic strategy for the two natural products, we obtained the compound DCZ0801, which was previously found to have anti-multiple myeloma activity. We performed both in vitro and in vivo assays to investigate its bioactivity and explore its underlying mechanism against DLBCL cells. The results showed that DCZ0801 treatment gave rise to a dose- and time-dependent inhibition of cell viability as determined by CCK-8 assay and flow cytometry assay. Western blot analysis results showed that the expression of caspase-3, caspase-8, caspase-9 and Bax was increased, while BCL-2 and BCL-XL levels were decreased, which suggested that DCZ0801 inhibited cell proliferation and promoted intrinsic apoptosis. In addition, DCZ0801 induced G0/G1 phase arrest by downregulating the protein expression levels of CDK4, CDK6 and cyclin D1. Furthermore, DCZ0801 exerted an anti-tumor effect by down-regulating the expressions of p-PI3K and p-AKT. There also existed a trend that the expression of p-JNK and p-P38 was restrained. Intraperitoneal injection of DCZ0801 suppressed tumor development in xenograft mouse models. The preliminary metabolic study showed that DCZ0801 displayed a rapid metabolism within 30 min. These results demonstrated that DCZ0801 may be a new potential anti-DLBCL agent in DLBCL therapy.

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