scholarly journals Smart stimuli-responsive biofunctionalized niosomal nanocarriers for programmed release of bioactive compounds into cancer cells in vitro and in vivo

2021 ◽  
Vol 10 (1) ◽  
pp. 1895-1911
Author(s):  
Najmeh Alsadat Abtahi ◽  
Seyed Morteza Naghib ◽  
Fatemeh Haghiralsadat ◽  
Javad Zavar Reza ◽  
Fatemeh Hakimian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Tumor Model ◽  
Tween 80 ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Mouse Tumor ◽  
Transfection Efficacy

Abstract Cancer treatment is challenging due to late-stage diagnosis, drug resistance and systemic toxicity of chemotherapeutic agents. The formulation of the drug into nanoparticles (NPs) can enhance the treatment efficacy and effectiveness. Therefore, a new cationic niosomal formulation, which contains Tween 80, Tween 60, cholesterol and lysine amino acid as a platform model to enhance transfection efficacy and reach more acceptable stability, and curcumin (Cur) as a biological anti-cancer drug, are introduced. Here, the authors focused on the design and synthesis of novel lysine-mediated niosomal NPs for the effectual and controlled release of the antitumor agent, Cur, and turned to optimize niosome formulations, concerning the volume of cholesterol and surfactant to implement these anticancer agents, simultaneously. The characterization of NPs s was carried out and the results showed the successful synthesis of Cur-entrapped niosomal NPs with high efficacy, sufficient positive charges and a favorable size (95/33 nm). The in vitro studies have been performed to investigate the cytotoxicity, cellular uptake and apoptosis of normal and cancer cells treated by black niosome, free Cur and niosom-loaded Cur. The results showed that implementing agents by niosome caused enhanced cytotoxicity, uptake and anticancer activity in cancer cells in comparison with normal cells. Furthermore, the effect of this nanodrug was surveyed on the 4T1 xenografted Balb/C mouse tumor model. Cur delivery to cancer models caused a higher tumor inhibition rate than in other groups.

Cancer Targeted Nanoparticles Specifically Induce Apoptosis in Cancer Cells and Spare Normal Cells

2012 ◽  
Vol 65 (1) ◽  
pp. 5 ◽  
Author(s):  
Jagat R. Kanwar ◽  
Rupinder K. Kanwar ◽  
Ganesh Mahidhara ◽  
Chun Hei Antonio Cheung
Keyword(s):  
Adverse Effects ◽  
Cancer Cells ◽  
Modern Medicine ◽  
Chemotherapeutic Agents ◽  
Locked Nucleic Acid ◽  
Cancer Drug ◽  
Drug Induced ◽  
Normal Cells

Curing cancer is the greatest challenge for modern medicine and finding ways to minimize the adverse effects caused by chemotherapeutic agents is of importance in improving patient’s physical conditions. Traditionally, chemotherapy can induce various adverse effects, and these effects are mostly caused by the non-target specific properties of the chemotherapeutic compounds. Recently, the use of nanoparticles has been found to be capable of minimizing these drug-induced adverse effects in animals and in patients during cancer treatment. The use of nanoparticles allows various chemotherapeutic drugs to be targeted to cancer cells with lower dosages. In addition to this, the use of nanoparticles also allows various drugs to be administered to the subjects by an oral route. Here, locked nucleic acid (LNA)-modified epithelial cell adhesion molecules (EpCAM), aptamers (RNA nucleotide), and nucleolin (DNA nucleotide) aptamers have been developed and conjugated on anti-cancer drug-loaded nanocarriers for specific delivery to cancer cells and spare normal cells. Significant amounts of the drug loaded nanocarriers (92 ± 6 %) were found to distribute to the cancer cells at the tumour site and more interestingly, normal cells were unaffected in vitro and in vivo. In this review, the benefits of using nanoparticle-coated drugs in various cancer treatments are discussed. Various nanoparticles that have been tried in improving the target specificity and potency of chemotherapeutic compounds are also described.

scholarly journals Apoptin Mediates Endogenous Mitophagy and Apoptosis by Regulating the Level of ROS in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yiquan Li ◽  
Chao Shang ◽  
Zirui Liu ◽  
Jicheng Han ◽  
Wenjie Li ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Tumor Model ◽  
Activation Mechanism ◽  
Mouse Tumor ◽  
Liver Cancer Cells ◽  
Key Factor

Abstract Background: Apoptin, as a tumor-specific pro-apoptotic protein, apoptin plays an important role in the field of anti-tumor, but its autophagy activation mechanism and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by apoptin and the interaction between autophagy and apoptosis. Methods: Through crystal violet staining and CCK-8 assay, we analyzed the effect of apoptin in inhibiting liver cancer in vitro, and also analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by apoptin. Subsequently, the relationship between apoptosis and autophagy induced by apoptin was analyzed. Then, flow cytometry was used to analyze the effect of ROS on apoptosis and autophagy mediated by apoptin. Then, the affect of ROS on apoptosis and autophagy mediated by apoptin was analyzed. Finally, the key genes leading to autophagy were analyzed by silencing different genes.Results: The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and apoptin can cause mitophagy through the increase of NIX protein. Apoptin can also significantly reduce the level of cellular ROS, which is related to the autophagy and apoptosis of liver cancer cells caused by apoptin. The change of ROS may be a key factor causing apoptosis and autophagy. Conclusion: The above results indicate that the increase of ROS level after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, which leads to endogenous apoptosis and mitophagy while recruiting NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and mitophagy induced by apoptin in liver cancer cells.

scholarly journals Antitumor Potential of Marine and Freshwater Lectins

Marine Drugs ◽  
2019 ◽  
Vol 18 (1) ◽  
pp. 11 ◽  
Author(s):  
Elena Catanzaro ◽  
Cinzia Calcabrini ◽  
Anupam Bishayee ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Complete Healing ◽  
Anticancer Compounds ◽  
Freshwater Organisms ◽  
Regulated Cell Death ◽  
Antitumor Potential ◽  
Unique Source

Often, even the most effective antineoplastic drugs currently used in clinic do not efficiently allow complete healing due to the related toxicity. The reason for the toxicity lies in the lack of selectivity for cancer cells of the vast majority of anticancer agents. Thus, the need for new potent anticancer compounds characterized by a better toxicological profile is compelling. Lectins belong to a particular class of non-immunogenic glycoproteins and have the characteristics to selectively bind specific sugar sequences on the surface of cells. This property is exploited to exclusively bind cancer cells and exert antitumor activity through the induction of different forms of regulated cell death and the inhibition of cancer cell proliferation. Thanks to the extraordinary biodiversity, marine environments represent a unique source of active natural compounds with anticancer potential. Several marine and freshwater organisms, ranging from the simplest alga to the most complex vertebrate, are amazingly enriched in these proteins. Remarkably, all studies gathered in this review show the impressive anticancer effect of each studied marine lectin combined with irrelevant toxicity in vitro and in vivo and pave the way to design clinical trials to assess the real antineoplastic potential of these promising proteins. It provides a concise and precise description of the experimental results, their interpretation as well as the experimental conclusions that can be drawn.

scholarly journals Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

2020 ◽  
Vol 117 (51) ◽  
pp. 32370-32379
Author(s):  
Olga A. Patutina ◽  
Svetlana K. Gaponova (Miroshnichenko) ◽  
Aleksandra V. Sen’kova ◽  
Innokenty A. Savin ◽  
Daniil V. Gladkikh ◽  
...  
Keyword(s):  
Tumor Model ◽  
Rnase H ◽  
Mouse Tumor ◽  
Internal Organs ◽  
Potent Inhibition ◽  
Nuclease Resistance ◽  
New Type

The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21–targeted µ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21–regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of µ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of µ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology.

scholarly journals Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

2020 ◽  
Vol 21 (19) ◽  
pp. 7345 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Daniela Melnik ◽  
Sascha Kopp ◽  
Jayashree Sahana ◽  
Manfred Infanger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Tumor Model ◽  
Cancer Drug ◽  
Cancer Therapies

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity (µg) research might be an unusual method to combat the disease, but cancer biologists decided to harness the power of µg as an exceptional method to increase efficacy and precision of future breast cancer therapies. Numerous studies have indicated that µg has a great impact on cancer cells; by influencing proliferation, survival, and migration, it shifts breast cancer cells toward a less aggressive phenotype. In addition, through the de novo generation of tumor spheroids, µg research provides a reliable in vitro 3D tumor model for preclinical cancer drug development and to study various processes of cancer progression. In summary, µg has become an important tool in understanding and influencing breast cancer biology.

scholarly journals Low dose amiodarone reduces tumor growth and angiogenesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eliana Steinberg ◽  
Arnon Fluksman ◽  
Chalom Zemmour ◽  
Katerina Tischenko ◽  
Adi Karsch-Bluman ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Low Dose ◽  
Tumor Model ◽  
In Vitro Assays ◽  
Potential Candidate ◽  
Key Factor ◽  
Angiogenic Effect

Abstract Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug’s harmful side effects.

scholarly journals A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Komakech ◽  
Youngmin Kang ◽  
Jun-Hwan Lee ◽  
Francis Omujal
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Treatment Options ◽  
Chemotherapeutic Agents ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Prostate Cancer Cells ◽  
Prunus Africana

Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

scholarly journals Anticancer and Anti-Inflammatory Activities of a Standardized Dichloromethane Extract fromPiper umbellatumL. Leaves

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Leilane Hespporte Iwamoto ◽  
Débora Barbosa Vendramini-Costa ◽  
Paula Araújo Monteiro ◽  
Ana Lúcia Tasca Gois Ruiz ◽  
Ilza Maria de Oliveira Sousa ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Tumor Model ◽  
Oral Route ◽  
Paw Edema ◽  
Anti Inflammatory ◽  
Cancer And Inflammation

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research onPiper umbellatumspecies, here we describe the anticancer (in vitroantiproliferative activity andin vivoEhrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) fromP. umbellatumleaves, containing 23.9% of 4-nerolidylcatechol. SDE showedin vitroandin vivoantiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE fromPiper umbellatumleaves could involve antiproliferative and anti-inflammatory effects. These findings highlightP. umbellatumas a source of compounds against cancer and inflammation.

scholarly journals MicroRNA-373-3p inhibits the growth of cervical cancer by targeting AKT1 both in vitro and in vivo

2021 ◽  
Author(s):  
Min-Min Yu ◽  
Gen-ju Wang ◽  
Kai-Hua Wu ◽  
Song-Lin Xue ◽  
Li- Li Ju ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Tumor Model ◽  
Cell Counting ◽  
Over Expression ◽  
Cervical Carcinoma Cell Line ◽  
Cervical Cancer Cells ◽  
Mrna And Protein Expression

Objective: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. Methods: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. Results: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. Conclusion: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.

scholarly journals Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12–IFN-γ

2017 ◽  
Vol 114 (43) ◽  
pp. 11482-11487 ◽  
Author(s):  
Madhuchhanda Kundu ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Cancer ◽  
Critical Role ◽  
Tumor Model ◽  
Cell Mediated Immunity ◽  
Ifn Γ

Cancer cells are adept at evading cell death, but the underlying mechanisms are poorly understood. IL-12 plays a critical role in the early inflammatory response to infection and in the generation of T-helper type 1 cells, favoring cell-mediated immunity. IL-12 is composed of two different subunits, p40 and p35. This study underlines the importance of IL-12 p40 monomer (p40) in helping cancer cells to escape cell death. We found that different mouse and human cancer cells produced greater levels of p40 than p40 homodimer (p402), IL-12, or IL-23. Similarly, the serum level of p40 was much greater in patients with prostate cancer than in healthy control subjects. Selective neutralization of p40, but not p402, by mAb stimulated death in different cancer cells in vitro and in vivo in a tumor model. Interestingly, p40 was involved in the arrest of IL-12 receptor (IL-12R) IL-12Rβ1, but not IL-12Rβ2, in the membrane, and that p40 neutralization induced the internalization of IL-12Rβ1 via caveolin and caused cancer cell death via the IL-12–IFN-γ pathway. These studies identify a role of p40 monomer in helping cancer cells to escape cell death via suppression of IL-12Rβ1 internalization.

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