Sensitization of tumor cells to chemotherapy by natural products: A systematic review of preclinical data and molecular mechanisms

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.

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Impact of Natural Dietary Agents on Multiple Myeloma Prevention and Treatment: Molecular Insights and Potential for Clinical Translation

Current Medicinal Chemistry ◽

10.2174/0929867325666180629153141 ◽

2020 ◽

Vol 27 (2) ◽

pp. 187-215 ◽

Cited By ~ 8

Author(s):

Lavinia Raimondi ◽

Angela De Luca ◽

Gianluca Giavaresi ◽

Agnese Barone ◽

Pierosandro Tagliaferri ◽

...

Keyword(s):

Signal Transduction ◽

Multiple Myeloma ◽

Natural Products ◽

Bone Disease ◽

Molecular Mechanisms ◽

Plasma Cells ◽

Hematologic Malignancy ◽

Signal Transduction Pathways ◽

Pharmacologically Active ◽

Dietary Agents

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.

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Adverse Effects of Natural Products: A Brief Pre-Systematic Review

Current Nutraceuticals ◽

10.2174/2665978601999200702163914 ◽

2020 ◽

Vol 01 ◽

Author(s):

Carla Pires ◽

Ana Fernandes

Keyword(s):

Systematic Review ◽

Adverse Event ◽

Natural Products ◽

Adverse Events ◽

In Vitro Study ◽

Google Scholar ◽

Inclusion Criteria ◽

Exclusion Criteria ◽

Meta Analyses

Background: Natural products are commonly used for treating health problems. These products may be associated with adverse events, which are defined as "noxious and unintended response to a medicinal product" by the European Medicine Agency. Objectives: To identify studies describing at least one adverse event (or with potential to promote an adverse event) related to the use of natural products, as well as to describe the involved product(s) and adverse event(s). Methods: A pre-systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Keywords: "natural product(s)" and ["adverse drug reaction(s)" or "adverse effect(s)"]. Screened databases: PubMed, SciELO, DOAJ and Google Scholar. Inclusion criteria: papers describing at least one adverse event associated with the use of natural products and published between 2017 and 2019. Exclusion criteria: Repeated studies, reviews and papers written in other languages than English, Portuguese, French or Spanish. Results: 104 studies were identified (20 PubMed; 0 SciELO; 2 DOAJ; 82 Google Scholar), but only 10 were selected (4 PubMed and 6 Google Scholar): 1 in-vitro study; 2 non-clinical studies, 1 study reporting in-vitro and clinical data and 5 studies were cases reports. Globally, 997 reports of adverse drug reactions with natural products were identified, mainly non-severe cases. Conclusion: Since a limited number of studies was found, we conclude that adverse events due to natural products may be underreported, or natural products may have a good safety profile. This review contributes for assuring the safety of natural products consumers, by evaluating the knowledge/information on the potential adverse events and interactions of these products.

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Molecular mechanisms of Zika virus teratogenesis from animal studies: a systematic review protocol

Systematic Reviews ◽

10.1186/s13643-021-01713-6 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Gabriela Elis Wachholz ◽

Julia do Amaral Gomes ◽

Juliano André Boquett ◽

Fernanda Sales Luiz Vianna ◽

Lavínia Schuler-Faccini ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Zika Virus ◽

Methodological Quality ◽

Molecular Mechanisms ◽

Grey Literature ◽

Standard Form ◽

Teratogenic Effect ◽

Control Group

Abstract Background Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability. Systematic review registration PROSPERO CRD42019157316

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Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

Scientific Reports ◽

10.1038/s41598-021-92515-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gautier Follain ◽

Naël Osmani ◽

Valentin Gensbittel ◽

Nandini Asokan ◽

Annabel Larnicol ◽

...

Keyword(s):

Blood Flow ◽

Tumor Cells ◽

Molecular Mechanisms ◽

Metastatic Progression ◽

Metastatic Dissemination ◽

Secondary Tumors ◽

Flow Profiles ◽

Endothelial Response ◽

Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

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The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18095038 ◽

2021 ◽

Vol 18 (9) ◽

pp. 5038

Author(s):

Andrea Maugeri ◽

Martina Barchitta ◽

Roberta Magnano San Lio ◽

Maria Clara La Rosa ◽

Claudia La Mastra ◽

...

Keyword(s):

Systematic Review ◽

Pilot Study ◽

Alcohol Consumption ◽

Telomere Length ◽

Molecular Mechanisms ◽

Epidemiological Studies ◽

Potential Association ◽

Significant Difference ◽

Periconceptional Period ◽

Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

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Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

International Journal of Molecular Sciences ◽

10.3390/ijms19113403 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3403 ◽

Cited By ~ 9

Author(s):

Xu Hu ◽

Dahong Li ◽

Chun Chu ◽

Xu Li ◽

Xianhua Wang ◽

...

Keyword(s):

Systematic Review ◽

Natural Products ◽

Drug Administration ◽

Antiproliferative Activity ◽

Natural Source ◽

Antiproliferative Effects ◽

Anti Cancer ◽

Ring Structures ◽

First Time ◽

Antiproliferative Activities

Alkaloids, a category of natural products with ring structures and nitrogen atoms, include most U.S. Food and Drug Administration approved plant derived anti-cancer agents. Evodiamine is an alkaloid with attractive multitargeting antiproliferative activity. Its high content in the natural source ensures its adequate supply on the market and guarantees further medicinal study. To the best of our knowledge, there is no systematic review about the antiproliferative effects of evodiamine derivatives. Therefore, in this article the review of the antiproliferative activities of evodiamine will be updated. More importantly, the antiproliferative activities of structurally modified new analogues of evodiamine will be summarized for the first time.

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Assessment of phagocytic activity in live macrophages-tumor cells co-cultures by Confocal and Nomarski Microscopy

Biology Methods and Protocols ◽

10.1093/biomethods/bpx002 ◽

2017 ◽

Vol 2 (1) ◽

Cited By ~ 5

Author(s):

Dalia Martinez-Marin ◽

Courtney Jarvis ◽

Thomas Nelius ◽

Stéphanie Filleur

Keyword(s):

Tumor Microenvironment ◽

Tumor Cells ◽

Phagocytic Activity ◽

Molecular Mechanisms ◽

Cell Types ◽

Functional Assay ◽

Loss Of Function ◽

Multiple Cancer

Abstract Macrophages have been recognized as the main inflammatory component of the tumor microenvironment. Although often considered as beneficial for tumor growth and disease progression, tumor-associated macrophages have also been shown to be detrimental to the tumor depending on the tumor microenvironment. Therefore, understanding the molecular interactions between macrophages and tumor cells in relation to macrophages functional activities such as phagocytosis is critical for a better comprehension of their tumor-modulating action. Still, the characterization of these molecular mechanisms in vivo remains complicated due to the extraordinary complexity of the tumor microenvironment and the broad range of tumor-associated macrophage functions. Thus, there is an increasing demand for in vitro methodologies to study the role of cell–cell interactions in the tumor microenvironment. In the present study, we have developed live co-cultures of macrophages and human prostate tumor cells to assess the phagocytic activity of macrophages using a combination of Confocal and Nomarski Microscopy. Using this model, we have emphasized that this is a sensitive, measurable, and highly reproducible functional assay. We have also highlighted that this assay can be applied to multiple cancer cell types and used as a selection tool for a variety of different types of phagocytosis agonists. Finally, combining with other studies such as gain/loss of function or signaling studies remains possible. A better understanding of the interactions between tumor cells and macrophages may lead to the identification of new therapeutic targets against cancer.

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Isolated Compounds from Natural Products with Potential Antidiabetic Activity - A Systematic Review

Current Diabetes Reviews ◽

10.2174/1573399813666170505120621 ◽

2017 ◽

Vol 14 (1) ◽

Cited By ~ 7

Author(s):

Antonio C.M. Munhoz ◽

Tania S. Frode

Keyword(s):

Systematic Review ◽

Natural Products ◽

Antidiabetic Activity

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The Role of Natural Products on Diabetes Mellitus Treatment: A Systematic Review of Randomized Controlled Trials

Pharmaceutics ◽

10.3390/pharmaceutics14010101 ◽

2022 ◽

Vol 14 (1) ◽

pp. 101

Author(s):

Lucía Vivó-Barrachina ◽

María José Rojas-Chacón ◽

Rocío Navarro-Salazar ◽

Victoria Belda-Sanchis ◽

Javier Pérez-Murillo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Natural Products ◽

Promising Therapeutic Target ◽

Prevalent Disease ◽

Bibliographic Search ◽

Treatment Of Diabetes ◽

Definition Of ◽

Diabetes Mellitus Treatment

The present study was carried out to relate the role of natural products in the metabolism of an increasingly prevalent disease, type 2 diabetes mellitus. At present, in addition to the pharmacological resources, an attempt is being made to treat diabetes mellitus with natural products. We carried out a systematic review of studies focusing on the role of natural products on diabetes mellitus treatment. The bibliographic search was done through Medline (Pubmed) and Web of Science. From 193 records, the title and summary of each were examined according to the criteria and whether they met the selection criteria. A total of 15 articles were included; after reviewing the literature, it is apparent that the concept of natural products is ambiguous as no clear boundary has been established between what is natural and what is synthetic, therefore we feel that a more explicit definition of the concept of “natural product” is needed. Gut microbiota is a promising therapeutic target in the treatment of diabetes. Therefore, it would be necessary to work on the relationship between the microbiome and the benefits in the treatment of diabetes mellitus. Treatment based solely on these natural products is not currently recommended as more studies are needed.

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