rosmarinic-acid and Neoplasms

Cancer is still the leading cause of death worldwide, burdening the global medical system. Rosmarinic acid (RA) is among the first secondary metabolites discovered and it is a bioactive compound identified in plants such as Boraginaceae and Nepetoideae subfamilies of the Lamiaceae family, including Thymus masticmasti chinaythia koreana, Ocimum sanctum, and Hyptis pectinate. This updated review is to highlight the chemopreventive and chemotherapeutic effects of RA and its derivatives, thus providing valuable clues for the potential development of some complementary drugs in the treatment of cancers. Relevant information about RA's chemopreventive and chemotherapeutic effects and its derivatives were collected from electronic scientific databases, such as PubMed/Medline, Scopus, TRIP database, Web of Science, and Science Direct. The results of the studies showed numerous significant biological effects such as antiviral, antibacterial, anti-inflammatory, anti-tumour, antioxidant and antiangiogenic effects. Most of the studies on the anticancer potential with the corresponding mechanisms are still in the experimental preclinical stage and are missing evidence from clinical trials to support the research. To open new anticancer therapeutic perspectives of RA and its derivatives, future clinical studies must elucidate the molecular mechanisms and targets of action in more detail, the human toxic potential and adverse effects.

Topics: Antioxidants; Cinnamates; Depsides; Humans; Lamiaceae; Neoplasms; Plant Extracts; Plants; Rosmarinic Acid

Phytochemicals are abundantly occurring natural compounds extracted from plant sources. Rosmarinic acid (RA) is an abundant phytochemical of

Topics: Antioxidants; Cinnamates; Diabetes Mellitus; Humans; Neoplasms; Neurodegenerative Diseases; Phytochemicals; Plant Extracts; Rosmarinic Acid

For decades, the use of secondary metabolites of various herbs has been an attractive strategy in combating human diseases. Rosmarinic acid (RA) is a bioactive phenolic compound commonly found in plants of Lamiaceae and Boraginaceae families. RA is biosynthesized using amino acids tyrosine and phenylalanine via enzyme-catalyzed reactions. However, the chemical synthesis of RA involves an esterification reaction between caffeic acid and 3,4-dihydroxy phenyl lactic acid contributing two phenolic rings to the structure of RA. Several studies have ascertained multiple therapeutic benefits of RA in various diseases, including cancer, diabetes, inflammatory disorders, neurodegenerative disorders, and liver diseases. Many previous scientific papers indicate that RA can be used as an anti-plasmodic, anti-viral and anti-bacterial drug. In addition, due to its high anti-oxidant capacity, this natural polyphenol has recently gained attention for its possible application as a nutraceutical compound in the food industry. Here we provide state-of-the-art, flexible therapeutic potential and biomedical features of RA, its implications and multiple uses. Along with various valuable applications in safeguarding human health, this review further summarizes the therapeutic advantages of RA in various human diseases, including cancer, diabetes, neurodegenerative diseases. Furthermore, the challenges associated with the clinical applicability of RA have also been discussed.

Topics: Cinnamates; Depsides; Humans; Lamiaceae; Neoplasms; Rosmarinic Acid

Cancer constitutes a severe threat to human health and quality of life and is one of the most significant causes of morbidity and mortality worldwide. Natural dietary products have drawn substantial attention in cancer treatment and prevention due to their availability and absence of toxicity. Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors. This review summarizes recent publications on culture techniques, extraction processes, and anti-tumor applications of RA-enriched dietary supplements. We discuss techniques to improve RA bioavailability and provide a mechanistic discussion of RA regarding tumor prevention, treatment, and adjuvant therapy. RA exhibits anticancer activity by regulating oxidative stress, chronic inflammation, cell cycle, apoptosis, and metastasis. These data suggest that daily use of RA-enriched dietary supplements can contribute to tumor prevention and treatment. RA has the potential for application in anti-tumor drug development.

Topics: Antineoplastic Agents; Antioxidants; Dietary Supplements; Humans; Neoplasms; Quality of Life; Rosmarinic Acid

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising target for the discovery of specific inhibitors as antitumor drugs. Based on the source of compounds, all LSD1 inhibitors in this review are divided into two categories: natural LSD1 inhibitors and synthetic LSD1 inhibitors. This review highlights the research progress of LSD1 inhibitors with the potential to treat cancer covering articles published in 2020. Design strategies, structure-activity relationships, co-crystal structure analysis and action mechanisms are also highlighted.

Topics: Antineoplastic Agents, Phytogenic; Enzyme Inhibitors; Histone Demethylases; Humans; Molecular Structure; Neoplasms

Rosmarinic acid (RA) is a highly valued natural phenolic compound that is very commonly found in plants of the families Lamiaceae and Boraginaceae, including Coleus blumei, Heliotropium foertherianum, Rosmarinus officinalis, Perilla frutescens, and Salvia officinalis. RA is also found in other members of higher plant families and in some fern and horned liverwort species. The biosynthesis of RA is catalyzed by the enzymes phenylalanine ammonia lyase and cytochrome P450-dependent hydroxylase using the amino acids tyrosine and phenylalanine. Chemically, RA can be produced via methods involving the esterification of 3,4-dihydroxyphenyllactic acid and caffeic acid. Some of the derivatives of RA include melitric acid, salvianolic acid, lithospermic acid, and yunnaneic acid. In plants, RA is known to have growth-promoting and defensive roles. Studies have elucidated the varied pharmacological potential of RA and its derived molecules, including anticancer, antiangiogenic, anti-inflammatory, antioxidant, and antimicrobial activities. The demand for RA is therefore, very high in the pharmaceutical industry, but this demand cannot be met by plants alone because RA content in plant organs is very low. Further, many plants that synthesize RA are under threat and near extinction owing to biodiversity loss caused by unscientific harvesting, over-collection, environmental changes, and other inherent features. Moreover, the chemical synthesis of RA is complicated and expensive. Alternative approaches using biotechnological methodologies could overcome these problems. This review provides the state of the art information on the chemistry, sources, and biosynthetic pathways of RA, as well as its anticancer properties against different cancer types. Biotechnological methods are also discussed for producing RA using plant cell, tissue, and organ cultures and hairy-root cultures using flasks and bioreactors. The recent developments and applications of the functional genomics approach and heterologous production of RA in microbes are also highlighted. This chapter will be of benefit to readers aiming to design studies on RA and its applicability as an anticancer agent.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biosynthetic Pathways; Biotechnology; Cinnamates; Depsides; Genomics; Humans; Neoplasms; Plants; Rosmarinic Acid

Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cinnamates; Depsides; Humans; Neoplasms; Phytotherapy; Plant Extracts; Plants, Medicinal; Polyphenols; Rosmarinic Acid; Rosmarinus; Signal Transduction; Xenograft Model Antitumor Assays

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Breast Neoplasms; Cinnamates; Depsides; Drug Interactions; Europe; Humans; Neoplasms; Phytotherapy; Plant Extracts; Rosmarinic Acid; Rosmarinus; Triterpenes; United States; United States Food and Drug Administration; Ursolic Acid

Ocimum sanctum L. or Ocimum tenuiflorum L, commonly known as the Holy Basil in English or Tulsi in the various Indian languages, is a important medicinal plant in the various traditional and folk systems of medicine in Southeast Asia. Scientific studies have shown it to possess antiinflammatory, analgesic, antipyretic, antidiabetic, hepatoprotective, hypolipidemic, antistress, and immunomodulatory activities. Preclinical studies have also shown that Tulsi and some of its phytochemicals eugenol, rosmarinic acid, apigenin, myretenal, luteolin, β-sitosterol, and carnosic acid prevented chemical-induced skin, liver, oral, and lung cancers and to mediate these effects by increasing the antioxidant activity, altering the gene expressions, inducing apoptosis, and inhibiting angiogenesis and metastasis. The aqueous extract of Tulsi and its flavanoids, orintin, and vicenin are shown to protect mice against γ-radiation-induced sickness and mortality and to selectively protect the normal tissues against the tumoricidal effects of radiation. The other important phytochemicals like eugenol, rosmarinic acid, apigenin, and carnosic acid are also shown to prevent radiation-induced DNA damage. This review summarizes the results related to the chemopreventive and radioprotective properties of Tulsi and also emphasizes aspects that warrant future research to establish its activity and utility in cancer prevention and treatment.

Topics: Abietanes; Animals; Apigenin; Cinnamates; Depsides; Disease Models, Animal; Drug Evaluation, Preclinical; Eugenol; Humans; Luteolin; Neoplasms; Ocimum; Phytochemicals; Plant Extracts; Plants, Medicinal; Rosmarinic Acid; Sitosterols

Mitogen-activated protein kinase-3 (MAPK3) is the upstream regulator in the MAPK cascade and is involved in many critical signaling pathways and biological processes, such as cell proliferation, survival, and apoptosis. MAPK3 overexpression is linked to onset, development, metastasis, and drug resistance in several human cancers. Thus, identifying novel and effective MAPK3 inhibitors is highly demanded. Herein, we aimed to discover organic compounds from cinnamic acid derivatives as potential MAPK3 inhibitors.. The binding affinity of 20 cinnamic acids to the MAPK3 active site was tested using the AutoDock 4.0 software. Top-ranked cinnamic acids were ranked based on the Δ. Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate might be helpful in cancer therapy by inhibiting MAPK3.

Topics: Caffeic Acids; Chlorogenic Acid; Glucosides; Humans; Neoplasms; Rosmarinic Acid

Rosmarinic acid (Ros) is one of phenolic metabolites with powerful potency as an anticancer agent, with different mechanisms to diminish the cancer cells. This current study represents radiolabeling of Ros with

Topics: Animals; Cinnamates; Depsides; Mice; Neoplasms; Rosmarinic Acid; Technetium; Tissue Distribution

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cinnamates; Depsides; Diterpenes; Humans; Neoplasms; Plant Roots; Plants, Medicinal; Rosmarinic Acid; Salvia

Rosmarinic acid is a natural polyphenolic compound that is found in different plant species and used for different medicinal purposes. This study aimed to investigate the chemo-preventive effect of rosmarinic acid and evaluate its antitumor efficacy alone or in combination with Paclitaxel in breast cancer mice model. Ehrlich induced mice mammary solid tumor model was used in the study. Mice were treated with oral rosmarinic acid and intraperitoneal Paclitaxel. Inflammation, angiogenesis, and apoptosis were checked. Enzyme linked immunosorbent assay (ELISA), quantitative real time PCR, and immunohistochemical methods were performed. Rosmarinic acid used prior to tumor induction suppressed NF-κB, TNF-α, vascular endothelial growth factor (VEGF) serum levels, and VEGF receptors. It also triggered apoptosis by restoring the levels of P53, Bcl-2, Bax, and caspase-3. Furthermore, in Ehrlich solid tumor mice, rosmarinic acid, and/or Paclitaxel significantly suppressed tumor growth with an increase in apoptotic markers P53 and Caspase-3 levels, and suppressed the Bcl2/Bax ratio. Rosmarinic acid exerted chemo-preventive and therapeutic potential alone or in combination with Paclitaxel. Moreover, rosmarinic acid targets numerous signaling pathways associated with breast cancer.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Caspase 3; Cinnamates; Depsides; Inflammation; Mice; Neoplasms; Neovascularization, Pathologic; NF-kappa B; Paclitaxel; Rosmarinic Acid; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A

Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure.

Topics: Antibiotics, Antineoplastic; Apoptosis; Cardiotoxicity; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cinnamates; Depsides; Doxorubicin; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Neoplasms; Rosmarinic Acid

Microtubule affinity regulating kinase (MARK4) is a potential drug target for different types of cancer as it controls the early step of cell division. In this study, we have screened a series of natural compounds and finally identified rosmarinic acid (RA) as a potential inhibitor of MARK4. Molecular docking and 500 ns all-atom simulation studies suggested that RA binds to the active site pocket of MARK4, forming enough number of non-covalent interactions with critical residues and MARK4-RA complex is stable throughout the simulation trajectory. RA shows an excellent binding affinity to the MARK4 with a binding constant (K) of 10

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cinnamates; Depsides; HEK293 Cells; Humans; Molecular Docking Simulation; Neoplasms; Phosphorylation; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Rosmarinic Acid; tau Proteins

Nowadays, healthy eating is increasing the demand of functional foods by societies as sources of bioactive products with healthy qualities. For this reason, we tested the safety of the consumption of Borago officinalis L. and its main phenolic components as well as the possibility of its use as a nutraceutical plant to help in cancer prevention. The in vivo Drosophila Somatic Mutation and Recombination Test (SMART) and in vitro HL-60 human cell systems were performed, as well-recognized methods for testing genotoxicity/cytotoxicity of bioactive compounds and plant products. B. officinalis and the tested compounds possess antigenotoxic activity. Moreover, B. officinalis wild type cultivar exerts the most antigenotoxic values. Cytotoxic effect was probed for both cultivars with IC50 values of 0.49 and 0.28 mg · mL(-1) for wild type and cultivated plants respectively, as well as their constituent rosmarinic acid and the assayed phenolic mixture (IC50 = 0.07 and 0.04 mM respectively). B. officinalis exerts DNA protection and anticarcinogenic effects as do its component rosmarinic acid and the mixture of the main phenolics presented in the plant. In conclusion, the results showed that B. officinalis may represent a high value plant for pleiotropic uses and support its consumption as a nutraceutical plant.

Topics: Animals; Anticarcinogenic Agents; Biological Availability; Borago; Cinnamates; Cytotoxicity, Immunologic; Cytotoxins; Depsides; HL-60 Cells; Humans; Inhibitory Concentration 50; Mutagenicity Tests; Neoplasms; Phenols; Rosmarinic Acid

The leaves of Rosmarinus officinalis harvested from three different locations of Turkey were extracted by both methanolic and supercritical CO(2) extraction. Subsequently, six extracts and the active compounds, carnosic acid, and rosmarinic acid were applied to various human cancer cell lines including NCI-H82 (human, small cell lung, carcinoma), DU-145 (human, prostate, carcinoma), Hep-3B (human, black, liver, carcinoma, hepatocellular), K-562 (human chronic myeloid leukemia), MCF-7 (human, breast, adenocarcinoma), PC-3 (human, prostate, adenocarcinoma) and MDA-MB-231 (human, breast, adenocarcinoma) by MTT assay. Supercritical CO(2) extracts had superior antiproliferative effect compared to the soxhlet extracts. Although the extracts exhibited various cytotoxic effects against different cell lines, comparatively low IC(50) values ranging between 12.50 and 47.55 microg/ml were attained against K-562, being the most sensitive cell line. Moreover, carnosic acid caused the lowest cell viability with values ranging from 13 to 30 % at a concentration of 19 muM after 48 h of treatments, resulting in superior antiproliferative effect. Rosemary extract is a potential candidate to be included in the anti-cancer diet with pre-determined doses avoiding toxicity.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cinnamates; Depsides; Humans; Inhibitory Concentration 50; Neoplasms; Phytotherapy; Plant Extracts; Rosmarinic Acid; Rosmarinus; Turkey