Effects of propolis and its bioactive components on breast cancer cell pathways and the molecular mechanisms involved

2021 ◽  
pp. 1-11
Author(s):  
Rina Masadah ◽  
Dzul Ikram ◽  
Syahrul Rauf

BACKGROUND: Breast cancer is a female malignancy that is a significant cause of mortality worldwide. Currently, investigations on natural ingredients as new candidates for chemopreventive agents and breast cancer chemotherapies are increasing. Propolis is a natural resinous material produced by honeybees that exhibit anticancer potential. Several studies have mentioned the major bioactive compounds of propolis, but their mechanism of action is not clearly understood. OBJECTIVES: The purpose of this review is to collect and summarize the evidence related to the effectiveness of propolis and its bioactive contents as candidates for breast cancer therapy and analyze the molecular mechanisms involved in their therapeutic pathways. METHODS: We reviewed 94 articles from journals and databases, extracted the results, and produced summaries and conclusions. RESULTS: Propolis and its bioactive ingredients show cytotoxic, anti-proliferative, pro-autophagic, anti-metastatic, and antioxidant activities, as well as synergistic effects with chemotherapy or radiotherapy in breast cancer. Its therapeutic activity involves various target molecules, including NF-κβ, Fas receptors, p53, TLR4, ANXA7, and voltage-gated Na+ channel (VGSC). CONCLUSION: The bioactive components of propolis and the target molecules involved need to be explored further to develop new breast cancer therapies and overcome the problem of chemoradiation resistance.

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1050 ◽  
Author(s):  
Reem Saleh ◽  
Rowaida Z. Taha ◽  
Varun Sasidharan Nair ◽  
Nehad M. Alajez ◽  
Eyad Elkord

Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, which shows resistance to common breast cancer therapies, as it lacks the expression of the most common breast cancer targets. Therefore, TNBC treatment remains a challenge. Targeting programmed cell death-ligand 1 (PD-L1) by monoclonal antibodies (mAbs), for example, atezolizumab, has revolutionized the treatment for various cancer types. However, the therapeutic efficacy of targeting PD-L1 in TNBC is currently under investigation. In this study, we investigated the molecular mechanisms by which the human TNBC cell line MDA-MB-231, expressing PD-L1, responds to atezolizumab, using RNA-Seq. Transcriptome analysis revealed 388 upregulated and 362 downregulated genes in response to atezolizumab treatment. The expression of selected genes, from RNA-Seq data, was subsequently validated using RT-qPCR in the MDA-MB-231 and MDA-MB-468 TNBC cells following atezolizumab treatment. Bioinformatics analysis revealed that atezolizumab downregulates genes promoting cell migration/invasion and metastasis, epithelial-mesenchymal transition (EMT), cell growth/proliferation/survival, and hypoxia. On the contrary, genes associated with apoptosis and DNA repair were upregulated in response to atezolizumab treatment. Gene set enrichment analyses revealed that a significant number of these genes are related to the NF-kB, PI3K/Akt/mTOR, MAPK, and CD40 signaling pathways. Using functional assays, we confirmed that atezolizumab increases MDA-MB-231 cell apoptosis/necrosis, and reduces their proliferation and viability. Collectively, our findings provide novel insights into the molecular mechanisms/signaling pathways by which atezolizumab exerts inhibitory effects on TNBC, thereby inhibiting EMT/metastasis, tumor growth/survival, and the induction of hypoxia.


2014 ◽  
Vol 7 ◽  
pp. CGM.S11288 ◽  
Author(s):  
Kristin R. Landis-Piwowar ◽  
Neena R. Iyer

The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Moreover, phytochemicals are capable of interfering with the molecular mechanisms of metastasis. Likewise, numerous synthetic compounds are relevant and clinically viable as chemopreventive agents during the fundamental stages of carcinogenesis. While molecularly targeted anti-cancer therapies are in constant stages of development, superior patient outcomes are observed if carcinogenic processes are prevented altogether. This article reviews the role of chemopreventive compounds in inhibition of cancer initiation and their ability to reduce cancer progression.


2020 ◽  
Vol 21 (21) ◽  
pp. 7836
Author(s):  
Stefania Cocco ◽  
Alessandra Leone ◽  
Michela Piezzo ◽  
Roberta Caputo ◽  
Vincenzo Di Lauro ◽  
...  

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development. Autophagy is a highly conserved homeostatic process that can be activated in response to antineoplastic agents as a cytoprotective mechanism. Inhibition of autophagy could enhance tumor cell death by diverse anti-cancer therapies, representing an attractive approach to control mechanisms of drug resistance. In this manuscript, we present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.


2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Katarzyna Walczak ◽  
Sebastian Marciniak ◽  
Grażyna Rajtar

The effect of diet on cancer formation and prevention of carcinogenesis has attracted considerable attention for years and is the subject of several studies. Some components of the daily diet, such as resveratrol, curcumin, genistein, gingerol, can significantly reduce the risk of cancer or affect the rate of tumor progression. Cancer chemoprevention assumes the use of natural or synthetic biologically active substances in order to prevent, inhibit or reverse the progression of cancer. There are many biologically active compounds in several natural products, i.e. garlic, ginger, soy, curcuma, tomatoes, cruciferous plants or green tea. Their chemopreventive activity is based on the inhibition of processes underlying carcinogenesis (inflammation, transformation and proliferation), but also affects the final phase of carcinogenesis - angiogenesis and metastasis. Despite the relatively low toxicity of chemopreventive agents, their molecular targets often coincide with the objectives of the currently used cancer therapies. The widespread use of chemopreventive agents may contribute to reduction of the rate of cancer incidence, and increase the effectiveness of conventional cancer therapies. In the present study, selected molecular mechanisms of the chemopreventive activity have been discussed, especially their involvement in the regulation of signal transduction, cell cycle regulation, apoptosis, metastasis and angiogenesis. The role of chemopreventive agents in the inflammatory process, the metabolism of xenobiotics and multidrug resistance has been also characterized.


2019 ◽  
Vol 30 (3) ◽  
pp. 16-22

World Health Organization (WHO) estimated that 80% of the population of developing countries use traditional medicines, mostly natural plant products, for their primary health care needs. In the past few decades, the medicinal value of plants has been assumed more important dimension owing largely to the discovery that extracts from plants contain not only primary metabolites but also a diverse array of secondary metabolites with antioxidant potential. Medicinal plants are potential sources of natural compounds with biological activities and therefore attract the attention of researchers worldwide. Antioxidants are vital substances which possess ability to protect the body from damage due to free radical-induced oxidative stress. The purpose of current study was to determine the antioxidant activities and bioactive components of Foeniculum vulgare (fennel) (Samonsabar) seeds by using UV Visible Spectrophotometer (UV-Vis) and Gas Chromatography-Mass Spectrometry (GC-MS). Aqueous extract of fennel seeds showed more antioxidant activity (IC50: 0.28 ug/ml) than ethanolic extract (IC50: 0.83 ug/ml) and comparable to standard antioxidant, ascorbic acid (IC50: 0.59 ug/ml). GC-MS analysis was fruitful in identification of compounds based on peak area, retention time, molecular formula, molecular weight, MS Fragmentions and pharmacological actions. Ten bioactive phytochemical compounds from aqueous extracts and 11 from ethanolic extract of fennel seeds were identified. These findings indicated that fennel seeds are potential to provide preventive properties against oxidative damage. These results will give scientific information for quality control of indigenous drug to herbal medicine users and local practitioners using fennel for different types of ailments


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