scholarly journals Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 747
Author(s):  
Eleonora Turrini ◽  
Piero Sestili ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioactive Molecules ◽  
Piper Nigrum ◽  
Comprehensive Overview ◽  
Anticancer Properties ◽  
Toxicological Profile ◽  
Key Pathways ◽  
New Anticancer Drugs

The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients.

scholarly journals Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

2021 ◽  
Vol 23 (1) ◽  
pp. 122
Author(s):  
Dongwei Wu ◽  
Johanna Berg ◽  
Birte Arlt ◽  
Viola Röhrs ◽  
Munir A. Al-Zeer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Early Death ◽  
Human Kidney ◽  
Therapeutic Window ◽  
Cancer Model ◽  
Cell Type ◽  
Anaplastic Lymphoma ◽  
New Anticancer Drugs

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.

scholarly journals Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy

2020 ◽  
Vol 10 (14) ◽  
pp. 4732
Author(s):  
Sofia Kamlund ◽  
Birgit Janicke ◽  
Kersti Alm ◽  
Stina Oredsson
Keyword(s):  
Cell Proliferation ◽  
Fluorescence Microscopy ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Digital Holography ◽  
Cell Tracking ◽  
Population Based ◽  
Longitudinal Tracking ◽  
Long Time ◽  
New Anticancer Drugs

A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that small subpopulations of cells, reacting differently to the potential drug go undetected. This is a problem specifically related to the most aggressive single cancer cells in a tumor as they appear to be insensitive to the drugs used today. These cells are not detected in population-based studies when developing new anticancer drugs. Thus, to get a deeper understanding of how all individual cancer cells react to chemotherapeutic drugs, longitudinal tracking of individual cells is needed. Here we have used digital holography for long time imaging and longitudinal tracking of individual JIMT-1 breast cancer cells. To gain further knowledge about the tracked cells, we combined digital holography with fluorescence microscopy. We grouped the JIMT-1 cells into different subpopulations based on expression of CD24 and E-cadherin and analyzed cell proliferation and cell migration for 72 h. We investigated how the cancer stem cell (CSC) targeting drug salinomycin affected the different subpopulations. By uniquely combining digital holography with fluorescence microscopy we show that salinomycin specifically targeted the CD24− subpopulation, i.e., the CSCs, by inhibiting cell proliferation, which was evident already after 24 h of drug treatment. We further found that after salinomycin treatment, the surviving cells were more epithelial-like due to the selection of the CD24+ cells.

scholarly journals Exosomes and Cell Communication: From Tumour-Derived Exosomes and Their Role in Tumour Progression to the Use of Exosomal Cargo for Cancer Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 822
Author(s):  
Andrea Nicolini ◽  
Paola Ferrari ◽  
Pier Mario Biava
Keyword(s):  
Immune System ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Tumour Progression ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Cancer Development ◽  
Anticancer Properties ◽  
Natural Substances ◽  
Therapeutic Trials

Exosomes are nano-vesicle-shaped particles secreted by various cells, including cancer cells. Recently, the interest in exosomes among cancer researchers has grown enormously for their many potential roles, and many studies have focused on the bioactive molecules that they export as exosomal cargo. These molecules can function as biomarkers in diagnosis or play a relevant role in modulating the immune system and in promoting apoptosis, cancer development and progression. Others, considering exosomes potentially helpful for cancer treatment, have started to investigate them in experimental therapeutic trials. In this review, first, the biogenesis of exosomes and their main characteristics was briefly described. Then, the capability of tumour-derived exosomes and oncosomes in tumour microenvironments (TMEs) remodelling and pre-metastatic niche formation, as well as their interference with the immune system during cancer development, was examined. Finally, the potential role of exosomes for cancer therapy was discussed. Particularly, in addition, their use as carriers of natural substances and drugs with anticancer properties or carriers of boron neutron capture therapy (BNCT) and anticancer vaccines for immunotherapy, exosomes as biological reprogrammers of cancer cells have gained increased consensus. The principal aspects and the rationale of this intriguing therapeutic proposal are briefly considered.

Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: A Meta-Analysis

2014 ◽  
Vol 32 (32) ◽  
pp. 3634-3642 ◽  
Author(s):  
Saroj Niraula ◽  
Eitan Amir ◽  
Francisco Vera-Badillo ◽  
Bostjan Seruga ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Meta Analysis ◽  
Molecular Target ◽  
Chemotherapeutic Agents ◽  
Targeted Agents ◽  
Treatment Frequency ◽  
Experimental Drugs ◽  
Grade 3 ◽  
New Anticancer Drugs

Purpose There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management. Methods We identified anticancer drugs approved by the US Food and Drug Administration from 2000 to 2011 and pivotal trials supporting their registration. Twelve frequent grade 3 to 4 adverse event (AEs) were weighted and pooled in a meta-analysis. Estimates of incremental drug prices and incremental costs for management of AEs were calculated according to type of new agent based on target specificity. Results We identified 41 studies comprising 27,539 patients and evaluating 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had a lower incidence of grade 3 to 4 toxicities compared with controls (median risk ratio [RR], 0.67; P = .22), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR, 3.39; P < .001) and chemotherapeutic agents (median RR, 1.73; P < .001), were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR, 2.11; P < .001) or not (RR, 3.02; P < .001). Median incremental drug price for experimental agents was $6,000 per patient per month. Median cost of managing toxicity was low compared with drug costs but higher than controls for treatment with less-specific targeted agents and chemotherapies. Conclusion Newly approved anticancer drugs are associated with increased toxicity, except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less-selected patients treated in general oncologic practice. Development of biomarker-driven agents should be encouraged.

scholarly journals Natural Phytochemicals in Bladder Cancer Prevention and Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong Xia ◽  
Ruijiao Chen ◽  
Guangzhen Lu ◽  
Changlin Li ◽  
Sen Lian ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Anticancer Drugs ◽  
Anticancer Activities ◽  
First Line ◽  
Anticancer Properties ◽  
Bladder Cancer Cells ◽  
Cancer Types ◽  
Available Information ◽  
New Anticancer Drugs

Phytochemicals are natural small-molecule compounds derived from plants that have attracted attention for their anticancer activities. Some phytochemicals have been developed as first-line anticancer drugs, such as paclitaxel and vincristine. In addition, several phytochemicals show good tumor suppression functions in various cancer types. Bladder cancer is a malignant tumor of the urinary system. To date, few specific phytochemicals have been used for bladder cancer therapy, although many have been studied in bladder cancer cells and mouse models. Therefore, it is important to collate and summarize the available information on the role of phytochemicals in the prevention and treatment of bladder cancer. In this review, we summarize the effects of several phytochemicals including flavonoids, steroids, nitrogen compounds, and aromatic substances with anticancer properties and classify the mechanism of action of phytochemicals in bladder cancer. This review will contribute to facilitating the development of new anticancer drugs and strategies for the treatment of bladder cancer using phytochemicals.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Design of Lamivudine Loaded Nanoparticles for Oral Application by Nano Spray Drying Method: A New Approach to use an Antiretroviral Drug for Lung Cancer Treatment

2020 ◽  
Vol 23 (10) ◽  
pp. 1064-1079
Author(s):  
Ahmet Alper Öztürk ◽  
İrem Namlı ◽  
Kadri Güleç ◽  
Şennur Görgülü
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Cell Line ◽  
Anticancer Drugs ◽  
Release Kinetics ◽  
Prolonged Release ◽  
Lung Cancer Treatment ◽  
Anticancer Properties ◽  
Ft Ir

Aims: To prepare lamivudine (LAM)-loaded-nanoparticles (NPs) that can be used in lung cancer treatment. To change the antiviral indication of LAM to anticancer. Background: The development of anticancer drugs is a difficult process. One approach to accelerate the availability of drugs is to reclassify drugs approved for other conditions as anticancer. The most common route of administration of anticancer drugs is intravenous injection. Oral administration of anticancer drugs may considerably change current treatment modalities of chemotherapy and improve the life quality of cancer patients. There is also a potentially significant economic advantage. Objective: To characterize the LAM-loaded-NPs and examine the anticancer activity. Methods: LAM-loaded-NPs were prepared using Nano Spray-Dryer. Properties of NPs were elucidated by particle size (PS), polydispersity index (PDI), zeta potential (ZP), SEM, encapsulation efficiency (EE%), dissolution, release kinetics, DSC and FT-IR. Then, the anticancer activity of all NPs was examined. Results: The PS values of the LAM-loaded-NPs were between 373 and 486 nm. All NPs prepared have spherical structure and positive ZP. EE% was in a range of 61-79%. NPs showed prolonged release and the release kinetics fitted to the Weibull model. NPs structures were clarified by DSC and FT-IR analysis. The results showed that the properties of NPs were directly related to the drug:polymer ratio of feed solution. NPs have potential anticancer properties against A549 cell line at low concentrations and non-toxic to CCD 19-Lu cell line. Conclusion: NPs have potential anticancer properties against human lung adenocarcinoma cells and may induce cell death effectively and be a potent modality to treat this type of cancer. These experiments also indicate that our formulations are non-toxic to normal cells. It is clear that this study would bring a new perspective to cancer therapy.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

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