The role and possible mechanisms of action of propolis and its flavonoids in regulation of inflammatory pathways by (i) antioxidative and radical scavenging activities, (ii) regulation of cellular activities of inflammatory cells, (iii) modulation of the enzymes involved in arachidonic acid metabolism (phospholipase A2, cyclooxygenase, and lipoxygenase) and nitric oxide synthase, (iv) modulation of the release of other pro-inflammatory molecules, and (v) transcriptional modulation of proinflammatory genes are shown. official website and that any information you provide is encrypted Antitumor activity of Chinese propolis in human breast cancer MCF-7 and MDA-MB-231 cells. Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C. Mendez-Pfeiffer P., Juarez J., Hernandez J., et al. The influence of propolis and its components on cell proliferation. Xuan H., Li Z., Yan H., et al. It is used for the protection from infections, to seal gaps, openings in the hive, and toughen combs, and also, propolis is used to maintain the hive's internal temperature, leveling the beehive surface to protect from abnormal weather and predators [12]. Angiogenesis or neovascularization is the development of fresh blood vessels from present ones, and this process is very important to regulate the growth and maintenance of metastatic tumors [104]. Propolis: Types, composition, biological activities, and veterinary product patent prospecting. All of this evidence suggests that CAPE induces apoptosis in human multiple myeloma cells via oxidative stress [59]. Please enable it to take advantage of the complete set of features! It also promotes apoptosis in NPC cells by downregulating the expression of antiapoptotic proteins Bcl-xL, elevating the expression of proapoptotic proteins Bax, and generating PARP cleavage [46]. 2022 Jun 17;2022:5901191. doi: 10.1155/2022/5901191. Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C. Kimoto T., Koya-Miyata S., Hino K., et al. Regulation of apoptosis via propolis and its compounds. Recent Progress in Medicinal Plants. 2022 Nov 16;7(47):43055-43067. doi: 10.1021/acsomega.2c05368. Bielenberg D. R., Zetter B. R. The contribution of angiogenesis to the process of metastasis. Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF) using an in vivo cocktail approach. The .gov means its official. Median. Clinical trials require standardized quality control and perfect design, and metabolomics is widely regarded to help achieve these goals. The investigation of the biological activities of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties, especially in the research on new antineoplastic agents. Shahinozzaman M., Taira N., Ishii T., Halim M. A., Hossain M. A., Tawata S. Anti-inflammatory, anti-diabetic, and anti-alzheimers effects of prenylated flavonoids from okinawa propolis: an investigation by experimental and computational studies. J Pharmacol Exp Ther. Res. doi: 10.1016/j.jsbmb.2019.02.016. eCollection 2022 Nov 29. government site. Gaziano R., Moroni G., Bue C., Miele M. T., Sinibaldi-Vallebona P., Pica F. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: evidence and perspectives. Propolis exerts anticancer effects primarily by inhibiting cancer cell proliferation, inducing apoptosis through regulating various signaling pathways and arresting the tumor cell cycle, inducing autophagy, epigenetic modulations, and further inhibiting the invasion and metastasis of tumors. 2023 Jan 18;11(2):259. doi: 10.3390/biomedicines11020259. The CAPE significantly repressed the activation of signal transducer and activator of transcription-3 (STAT-3) in HEp-2 cells. The role of propolis and its compounds in the regulation of signaling pathways crucial for metastasis. J Diet Suppl. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Nutrients. 2022 Oct 8;27(19):6694. doi: 10.3390/molecules27196694. The green arrow points out the upregulation of signaling molecules, while the red arrow indicates the downregulation of molecular targets. [67]. Conclusion: During the first year of the . 2018;124:27852800. The HPLC-MS (high-performance liquid chromatography-mass spectrometry) and ultra-PLC-MS analyses have identified the predominant bioactive components in propolis such as chrysin, CAPE, artepillin C, nemorosone, galangin, cardanol, cardol, quercetin, kaempferol, and p-coumaric acid in Brazilian green propolis [36]. Propolis phytoconstituents differ depending on the source. The VEGF expression significantly decreased in CAPE-treated colon cancer cells (CT26) and also inhibited the synthesis of prostaglandin E2. Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. This clinical trial comprised a total of 135 individuals. Furthermore, OP treatment decreases the COX-2 activity and nitrite accumulation in lipopolysaccharide-induced inflammatory model, RAW264.7 cells [47]. Bestwick C. S., Milne L. Influence of galangin on HL-60 cell proliferation and survival. Oral propolis, nutritional status and quality of life with chemotherapy for breast cancer: a randomized, double-blind clinical trial. J Pharm Pharmacol. Izuta H., Shimazawa M., Tsuruma K., Araki Y., Mishima S., Hara H. Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Keywords: 55113. Experimental Evidence for Therapeutic Potentials of Propolis. 2006 Jan-Mar;7(1):22-31. Frion-Herrera Y., Diaz-Garcia A., Ruiz-Fuentes J., Rodriguez-Sanchez H., Sforcin J. M. The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation. Assessment of the radioprotective effect of propolis in breast cancer patients undergoing radiotherapy: new perspective for an old honey bee product. This review covered ScienceDirect, Scopus, Pubmed, and Scielo databases, as updated on October 2021. Acta Med. Epub 2015 Feb 27. The Wnt signaling is a primordial and evolutionarily conserved pathway that controls cell differentiation, proliferation, and migration [39]. The CAPE administration in HCT16 and human colon cancer cell lines suppressed the Wnt signaling pathway [29]. Combination treatment of docetaxel with caffeic acid phenethyl ester suppresses the survival and the proliferation of docetaxel-resistant prostate cancer cells via induction of apoptosis and metabolism interference. and transmitted securely. The honeybee products like honey, beeswax, bee venom, and bee pollen have been used as traditional medicine and also exhibited antimicrobial, antioxidant, anti-inflammatory, and anticancer properties in several preclinical studies in cell line and animal experiments [1317]. All the OP compounds have better absorption and bioavailability [47]. The findings of a recent randomized, double-blind, and placebo-controlled clinical trial compared propolis to a placebo on nutritional status and quality of life in breast cancer patients after chemotherapy. Oxidant/antioxidant properties of Croatian native propolis. The bioavailability of these main bioactive chemicals was then examined. Improving productivity in rabbits by using some natural feed additives under hot environmental conditions - A review. El-Seedi H. R., Eid N., Abd El-Wahed A. The CAPE treatment showed the suppressed extracellular signal-regulated kinase (ERK) and Akt phosphorylation and decreased cyclin D expression in 3T3-L1 fibroblast cells [12]. Propolis is reported to possess an array of biological properties including anti-inflammatory, antioxidant, anti-cancer, and anti-diabetic as well as cardioprotective, hepatoprotective, renoprotective, and derma protective activities. Propolis is a mixture of resinous compounds containing beeswax and partially digested exudates from plants leaves and buds. Barlak Y., Deger O., Colak M., Karatayli S. C., Bozdayi A. M., Yucesan F. Effect of Turkish propolis extracts on proteome of prostate cancer cell line. Int J Mol Sci. government site. Propolis polyphenolic compounds are having anticarcinogenic activity, and in addition to this, well-known predominant bioactive components of propolis like CAPE, artepillin C, and chrysin can inhibit cancer cell growth in various malignancies [27, 3739]. Gismondi A., Canuti L., Grispo M., Canini A. Biochemical composition and antioxidant properties of lavandula angustifolia miller essential oil are shielded by propolis against UV radiations. This site needs JavaScript to work properly. Antimetastatic effect of propolis and its polyphenolic/flavonoid compounds. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. Ao M., Xiao X., Li Q. Efficacy and safety of compound Kushen injection combined with chemotherapy on postoperative patients with breast cancer: a meta-analysis of randomized controlled trials. Functional and Clinical Proteomic Exploration of Pancreatic Cancer - PubMed Increased oxidative stress can result, Interaction between propolis and its polyphenolic/flavonoid components and the intestinal microbiota. National Library of Medicine Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents. Docetaxel with CAPE inhibited the proliferation and survival of docetaxel-resistant prostate cancer cells via inhibiting Bcl-2 and c-Myc and induced metabolic interference and apoptosis. Genes Dis. Epub 2015 Feb 27. According to another recent study, the expression of GSK-3 suppressed Snail and the disruption of HDAC6-mediated vimentin protein stability inhibits the cell migration and invasion of TNBC by propolin G. Propolin G, which targets EMT, might be a contender for TNBC treatment [130]. Kimoto T., Koya S., Hino K., et al. Recently, propolis was shown to have anti-inflammatory and immunomodulatory activity and inhibits the PAK1. Chrysin increases p21 protein expression by stimulating the p38 mitogen-activated protein kinase activity that led to the inhibition of the cell cycle and suppresses the cell proliferation in of C6 glioma [28]. doi: 10.1042/CS20160935. Although propolis is a good source of minerals, amino acids, vitamins A, E, and B complex, and the biochemical compounds like bioflavonoids, phenols, aromatic compounds, and many other molecules, which possess hepatoprotective activity, anti-inflammatory, antiproliferative, antifungal, antibacterial, and antimicrobial qualities, the exact constituent of propolis is still unknown; hence, further research is required to find out the new compounds [31, 4951]. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy. Resins and balms are major components (5060%) in raw propolis. A recent study demonstrated that Chinese propolis (25, 50 & 100g/ml) treatment inhibits cell proliferation by targeting glycolysis enzymes and proinflammatory cytokines including TNF-, IL-6, and NLRP3 in the breast cancer cells [79]. However, the molecular mechanism via which GPR141 advances breast cancer remains elusive. The site is secure. Cusinato D. A. C., Martinez E. Z., Cintra M. T. C., et al. Daleprane J. Hwang H. J., Park H. J., Chung H. J., et al. Foods. [110] have reported the impact of CAPE treatment on fibrosarcoma cells' (HT1080) invasion and metastasis. 2023 Jun 8. doi: 10.1007/s12223-023-01064-w. Online ahead of print. Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway. Relationship between ROS, inflammation, cancer, and propolis compounds. The Algerian propolis extract-treated cells showed reduced cell proliferation and inhibited the cell adhesion by altering the fibrinogen in lung cancer [74]. Planta Med. Effects of caffeic acid phenethyl ester against multi-species cariogenic biofilms. Federal government websites often end in .gov or .mil. Controlled, physiological inflammation is a useful, adaptive response that plays an important role in protection against infection, tissue repair, and adaptation to stress, more exactly, in the establishment of disturbed homeostasis. Keywords: Bankova V. Recent trends and important developments in propolis research. Bees use it to seal gaps in the hive to keep out. Ahangari Z., Naseri M., Vatandoost F. Propolis: chemical composition and its applications in endodontics. Chemical characterization, antioxidant and cytotoxic activities of Brazilian red propolis. The goal of the most recent study was to synthesize poly-(lactide-co-glycolide) acid (PLGA) nanoparticles for the encapsulation of Sonoran propolis (SP) as a matrix to increase the solubility of their polyphenolic compounds and improve delivery, and assess its antiproliferative activity on cancer cells. In general, raw propolis is composed of around 50% resins, 30% waxes, 10% essential oils, 5% pollen, and 5% of various organic compounds [1, 8, 9].More than 300 constituents were identified in different samples [7-10] and new ones are still being recognized during chemical characterization of . The results showed that CAPE treatment can suppress mRNA and protein expression of MMP-2 and MMP-9 in fibrosarcoma cells. Epub 2023 Feb 23. Synergism between propolis and hyperthermal intraperitoneal chemotherapy with cisplatin on ehrlich ascites tumor in mice. Many of the therapeutic effects can be attributed to its immunomodulatory functions. A low dose combination of withaferin A and caffeic acid phenethyl ester possesses anti-metastatic potential in vitro: molecular targets and mechanisms. Liao H. F., Chen Y. Y., Liu J. J., et al. Shin S. A., Lee H. N., Choo G. S., Kim H. J., Che J. H., Jung J. Y. Ixeris dentata (thunb. 2022 Oct 7;13:975181. doi: 10.3389/fphar.2022.975181. Keywords: Propolis is a natural and sticky material, also known as bee glue, that honey bees (Apis mellifera) produce from saps, resins, and mucilages collected from various parts of the plant, such as leaves, flower buds, and tree barks, then mixing them with beeswax and several bee enzymes [1,2].The word propolis originates from ancient Greek, in which "pro" stands for "at the . Drug Metab. B. M., Majeti N. V. R. K., Singhal S. S. Therapeutic potential of natural antioxidants. It is used by bees as glue, a general-purpose sealer, and as draught-extruder for beehives. The activity levels of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human hepatocytes were tested by Sasaki et al. Propolis extracts have shown apoptosis-promoting potential against diverse cancer cell lines such as HeLa [87], prostate adenocarcinoma [88], basophilic leukemia [89], and human breast [90], to study the activation of caspase and inhibition of mast cell granulation [91]. Clipboard, Search History, and several other advanced features are temporarily unavailable. doi: 10.1002/jsfa.10024. Epub 2023 Feb 23. Comparative evaluation of antiproliferative effects of Brazilian green propolis, its main source Baccharis dracunculifolia, and their major constituents artepillin C and baccharin. 2018 Aug 26;10(9):1170. doi: 10.3390/nu10091170. The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review. Furthermore, Niyomtham et al. The chemical composition of propolis differs greatly among species of bees and depends on geographical and climatic factors, plant resources, and collecting seasons, and it requires a different experimental approach to evaluate their biological potential. Before The propolis is multifaceted, and the chemical composition differs according to bee species, geographical origin, and plants that stimulate the bee's biological activities [26, 27]. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Generally, Asians and Europeans use propolis largely in the management of many diseases [24, 25]. Salmas R. E., Gulhan M. F., Durdagi S., Sahna E., Abdullah H. I., Selamoglu Z. The Potential Use of Propolis as an Adjunctive Therapy in Breast Egyptian propolis contains a high level of flavonoids, phenolics, and dihydroflavonoids in propolis extract, and it has anticancer effects in vitro studies and inhibits tumor growth in Ehrlich ascites carcinoma (EAC) in mice model. The encapsulation of propolis has shown promising results for the protection of bioactive compounds, local and gradual release and masking the astringent taste. Careers. MeSH The information mentioned here is not offered as specific medical advice for any individual and . It is crucial to understand which propolis components are bioavailable in the human body. Would you like email updates of new search results? Pharmacokinetic properties of compounds present in Okinawa propolis (OP) were analyzed by molinspiration online toolkit to consider them as potent drug candidates based on its Lipinski's 5th rule [61]. The failure of drugs in clinical trials is frequently due to poor absorption and oral bioavailability of drugs [59]. Federal government websites often end in .gov or .mil. 2022 Mar 18;10(4):1367-1401. doi: 10.1016/j.gendis.2022.02.007. Disclaimer. The CAPE has the ability to promote apoptosis in breast cancer cell lines (MCF-7 and MDA-MB-231) [86]. Cancer is the second most life-threatening disease and has become a global health and economic problem worldwide. Unauthorized use of these marks is strictly prohibited. A number of factors induce the generation of high levels of reactive radicals (ROS), leading to oxidative stress (OS) and OS-induced inflammation. The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens. Pharmaceuticals (Basel). Bookshelf Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: an experimental and theoretical approach. The .gov means its official. PMC Bethesda, MD 20894, Web Policies The main chemical groups responsible for the various pharmacological properties and health-related uses. Propolis is a complex mixture made by bee-released and plant-derived compounds. Lipids. However, there is currently a lack of human clinical data, particularly in the field of cancer treatment. Sci. Patients who used propolis supplements had a considerably longer median disease-free lifetime. Conclusion: Among patients with cancer pain on strong opioid regime, acetaminophen may not improve pain control, or decrease total opioid use. The https:// ensures that you are connecting to the Chemopreventive and Chemotherapeutic Effect of Propolis and Its A recent report suggested that red propolis along with L-lysine reduces tumor angiogenesis and tumor growth in hamster cheek pouch walker 256 cancer cell-inoculated cancer model [95]. Interestingly, after CP treatment, the Hippo pathway was stimulated in Panc-1 cells, providing as a mechanism for CP's antipancreatic cancer activity [132]. However, the commercially existing drugs are only effective against certain types of tumor due to the complexity of cancer, particularly cancer signaling and angiogenesis [107]. Overall, all of the earlier findings suggested that components of OP could be a harmless and novel drug for Alzheimer's, diabetes, and inflammation treatment [47]. Clin Exp Reprod Med. Further investigation using AG490, a selective STAT-3 inhibitor, demonstrated that CAPE not only suppressed STAT-3 but also suppressed the expression of PLK-1 in HEp-2 cells, indicating that STAT-3 was likely involved in the regulation of PLK-1 in HEp-2 cells. This site needs JavaScript to work properly. Poormolaie N, Mohammadi M, Mir A, Asadi M, Kararoudi AN, Vahedian V, Rashidi M, Maroufi NF. Introduction. Propolis and its components participate in all steps of the metastatic spread from the primary tumor through numerous mechanisms. Chemoprevention with green propolis green propolis extracted in L-lysine versus carcinogenesis promotion with L-lysine in N-Butyl-N-[4-hydroxybutyl] nitrosamine (BBN) induced rat bladder cancer. The anticancer potential of Chinese propolis was studied on human breast cancer cells. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines . An official website of the United States government. Artepillin C, another form of propolis, is reported to induce cytotoxicity through activating apoptosis and necrosis and inhibits mitosis in melanoma and carcinomas cells [1]. Received 2022 Mar 27; Accepted 2022 May 30. Propolis capsules (400 mg, 3 times daily) is consumed for 10 days before radiotherapy, 10 days during radiation treatment, and 10 days after irradiation. We intentionally did not include . Nutrients. Propolis: A Detailed Insight of Its Anticancer Molecular Mechanisms. Bouchelaghem S. Propolis characterization and antimicrobial activities against. Szliszka E, Zydowicz G, Janoszka B, Dobosz C, Kowalczyk-Ziomek G, Krol W. Int J Oncol. Bethesda, MD 20894, Web Policies Matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9 and intercellular adhesion molecule (ICAM) play important role in proteolytic degradation. Weng M. S., Ho Y. S., Lin J. K. Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression: involvement of p38 mitogen-activated protein kinase. Moreover, compound 5A was discovered to promote cell cycle arrest and apoptosis in CNE2 cells by inhibiting the expression of EGFR downstream signaling molecules in NPC cells [44]. The activity of CYP450 enzymes is crucial for therapeutic effectiveness since it has a major impact on the drug's concentration in circulation and its metabolites. Red propolis produces antioxidant effects, also inhibits angiogenesis through the modulation of angiogenic factors and inflammation, and reduces the levels of VEGF and HIF-1, and this shows the relationship between angiogenesis, oxidative stress, and tumor hypoxia [112, 113]. Brazilian green propolis induced apoptosis in human lung - PubMed Kumazawa S., Ueda R., Hamasaka T., Fukumoto S., Fujimoto T., Nakayama T. Antioxidant prenylated flavonoids from propolis collected in Okinawa, Japan. Asian Pac J Cancer Prev. Ethanolic propolis extract (250 or 500g/ml) treatment induces apoptosis in C6 glioma cells by increasing the mRNA expression of caspase-3, caspase-8, and caspase-9. Watanabe MA, Amarante MK, Conti BJ, Sforcin JM. In addition, natural ingredients of propolis induce a prominent reduction in CD4 + CD25 + FoxP3+ regulatory T cells that suppress antitumor activity by IL-10 or TGF- production. Choi S. M., Tucker D. F., Gross D. N., et al. and transmitted securely. The propolis composition differs based on the plant origin. The site is secure. Dunn I. F., Heese O., Black P. M. Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2023 Mar;50(1):12-18. doi: 10.5653/cerm.2022.05785. 2000 Nov;48(11):5226-30 Different types of Cuban propolis (red, brown and yellow) have been documented. Summary of the main biological activities of propolis. It has a wide spectrum of alleged applications including potential anti-infection and anticancer effects. Ning X., Ren X., Xie X., Yan P., Wang D., Huang X. Cytotoxicity Against Breast Cancer Cells Propolis has been shown to be cytotoxic against a wide range of breast cancer cells, namely BT-20, BT-474, BT-549, SKBR-3, MCF-7 . Kamiya T., Nishihara H., Hara H., Adachi T. Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress. Cancer chemoprevention by propolis and its polyphenolic compounds in experimental animals. The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity. STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. 8600 Rockville Pike Author Mahmoud Lotfy Khalil 1 Niyomtham N., Koontongkaew S., Yingyongnarongkul B. E., Utispan K. Tao L., Chen X., Zheng Y., et al. Interaction between propolis and its polyphenolic/flavonoid components and the intestinal microbiota. According to Kimoto et al., [63, 64] an antioxidative dosage of artepillin C prevented renal and pulmonary malignancies in male mice developed by ferric nitrilotriacetate. Elnakady Y. DL: death ligand, DR: death receptor, TNF-: tumor necrosis factor, FasL: Fas ligand, TRAIL: TNF-related apoptosis-inducing ligand, Bcl-2: B-cell lymphoma-2, Bad: Bcl-2-associated death promoter, Bax: Bcl-2-like protein, Apaf-1; apoptotic protease-activating factor 1. The site is secure. -, Stojanovi S., Najman S.J., Bogdanova-Popov B., Najman S.S. Propolis: Chemical composition, biological and pharmacological activityA Review. A. H. Targeting cancer metabolism and cell cycle by plant-derived compounds. Hence, this review summarizes the molecular targets and anticancer properties of propolis and its active compounds against various cancers. These results add to the current evidence available suggesting not to use acetaminophen as an adjuvant for advanced cancer patients with moderate to severe cancer pain who are on strong opioids. -, Kasote D., Bankova V., Viljoen A.M. Propolis: Chemical diversity and challenges in quality control. Propolis and its components exert a positive effect on the intestinal microbiota, leading to the establishment of intestinal homeostasis through improved gut health, healthy mucus layer, effective intestinal barrier, and functional gutmicrobiota axis.