Most cited article - PubMed ID 28524540
Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma
BACKGROUND: Cancer remains a major global health challenge, necessitating innovative prevention and treatment approaches. Certain plants, adapted to specific environments, may exhibit bioactive properties with potential anticancer applications. HYPOTHESIS: Seaberry (Hippophae rhamnoides L.) fruit peels may exert anticancer effects in breast carcinoma (BC) models through the additive or synergistic actions of their unique secondary metabolites. METHODS: H. rhamnoides fruit peel extracts were analyzed using the LC-DAD-MS and LC-DAD techniques to profile the content of carotenoids and flavonoids, respectively. The preclinical study evaluated seaberry fruit peel extracts in BC models: (1) a syngeneic 4T1 mouse breast adenocarcinoma model (triple-negative), (2) a rat model of chemically induced mammary carcinogenesis, and (3) in vitro studies with MCF-7 (hormone receptor-positive) and MDA-MB-231 (triple-negative) BC cell lines. RESULTS: LC-DAD-MS and LC-DAD analyses identified dominant metabolites, including isorhamnetin, quercetin glycosides, kaempferol glycosides, catechin, zeaxanthin, and lutein. In the 4T1 mouse model, seaberry treatment resulted in a significant, dose-dependent reduction in tumor volume (43% and 48% compared to controls) and a decrease in the mitotic activity index. Serum cytokine analysis showed dose-dependent reductions in IL-6, IL-10, and TNF-α. In the rat chemopreventive model, high-dose seaberry improved cancer prognosis by reducing the ratio of poorly differentiated tumors and increasing caspase-3 and Bax expression while decreasing Ki-67 and malondialdehyde levels. Both treatment doses elevated the Bax/Bcl-2 ratio and reduced the expression of cancer stem cell markers CD44, EpCam, and VEGF compared to controls. Epigenetic analyses revealed histone modifications (H4K16ac, H4K20me3) and altered methylation of tumor-suppressor genes (PITX2, RASSF1, PTEN, TIMP3). Microarray analysis (758 miRNAs) identified beneficial changes in nine oncogenic/tumor-suppressive miRNAs, including miR-10a-5p, miR-322-5p, miR-450a-5p, miR-142-5p, miR-148b-3p, miR-1839-3p, miR-18a-5p, miR-1949, and miR-347. In vitro, ethanolic seaberry extract conferred partial resistance to cisplatin-induced cytotoxicity in MCF-7 and MDA-MB-231 cells at IC50 concentrations. CONCLUSION: This study of H. rhamnoides in rodent BC models shows promising data but requires rigorous, long-term validation. Integrating plant-based nutraceuticals into oncology necessitates precise cancer-type profiling and patient stratification for effective personalized treatments.
- Keywords
- Hyppophae rhamnoides L., breast carcinoma, cancer stem cells, chemoprevention, epigenetics, rodent models, therapy modulation,
- Publication type
- Journal Article MeSH
INTRODUCTION: Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. HYPOTHESIS: Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. AIMS OF THE STUDY AND METHODS: Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. RESULTS: The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. CONCLUSION: This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.
- Keywords
- Aronia melanocarpa L., breast carcinoma, epigenetics, in vitro models, mechanism of action, rodent models,
- Publication type
- Journal Article MeSH
Introduction: Based on extensive data from oncology research, the use of phytochemicals or plant-based nutraceuticals is considered an innovative tool for cancer management. This research aimed to analyze the oncostatic properties of Salvia officinalis L. [Lamiaceae; Salviae officinalis herba] using animal and in vitro models of breast carcinoma (BC). Methods: The effects of dietary administered S. officinalis in two concentrations (0.1%/SAL 0.1/and 1%/SAL 1/) were assessed in both syngeneic 4T1 mouse and chemically induced rat models of BC. The histopathological and molecular evaluations of rodent carcinoma specimens were performed after the autopsy. Besides, numerous in vitro analyses using two human cancer cell lines were performed. Results and Conclusion: The dominant metabolites found in S. officinalis propylene glycol extract (SPGE) were representatives of phenolics, specifically rosmarinic, protocatechuic, and salicylic acids. Furthermore, the occurrence of triterpenoids ursolic and oleanolic acid was proved in SPGE. In a mouse model, a non-significant tumor volume decrease after S. officinalis treatment was associated with a significant reduction in the mitotic activity index of 4T1 tumors by 37.5% (SAL 0.1) and 31.5% (SAL 1) vs. controls (set as a blank group with not applied salvia in the diet). In addition, salvia at higher doses significantly decreased necrosis/whole tumor area ratio by 46% when compared to control tumor samples. In a rat chemoprevention study, S. officinalis at a higher dose significantly lengthened the latency of tumors by 8.5 days and significantly improved the high/low-grade carcinomas ratio vs. controls in both doses. Analyses of the mechanisms of anticancer activities of S. officinalis included well-validated prognostic, predictive, and diagnostic biomarkers that are applied in both oncology practice and preclinical investigation. Our assessment in vivo revealed numerous significant changes after a comparison of treated vs. untreated cancer cells. In this regard, we found an overexpression in caspase-3, an increased Bax/Bcl-2 ratio, and a decrease in MDA, ALDH1, and EpCam expression. In addition, salvia reduced TGF-β serum levels in rats (decrease in IL-6 and TNF-α levels were with borderline significance). Evaluation of epigenetic modifications in rat cancer specimens in vivo revealed a decline in the lysine methylations of H3K4m3 and an increase in lysine acetylation in H4K16ac levels in treated groups. Salvia decreased the relative levels of oncogenic miR21 and tumor-suppressive miR145 (miR210, miR22, miR34a, and miR155 were not significantly altered). The methylation of ATM and PTEN promoters was decreased after S. officinalis treatment (PITX2, RASSF1, and TIMP3 promoters were not altered). Analyzing plasma metabolomics profile in tumor-bearing rats, we found reduced levels of ketoacids derived from BCAAs after salvia treatment. In vitro analyses revealed significant anti-cancer effects of SPGE extract in MCF-7 and MDA-MB-231 cell lines (cytotoxicity, caspase-3/-7, Bcl-2, Annexin V/PI, cell cycle, BrdU, and mitochondrial membrane potential). Our study demonstrates the significant chemopreventive and treatment effects of salvia haulm using animal or in vitro BC models.
- Keywords
- Salvia officinalis L., apoptosis, breast carcinoma, cancer stem cells, cell proliferation, epigenetics, human carcinoma cell lines, inflammatory cytokines,
- Publication type
- Journal Article MeSH
Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper.
- Keywords
- breast cancer, cancer stem cells, non-responsiveness, predictive, preventive and personalised medicine, resistance, secondary and tertiary care,
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals' and patients' needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large.
- Keywords
- Breast cancer, COVID-19, Cost-effective disease management, Evidence-based research data, Food, Health risk assessment, Improved individual outcomes, Individualized patient profiling, Modifiable risk factors, Molecular patterns, Phytochemicals, Plants, Predictive Preventive Personalized Medicine (PPPM/3PM), Primary secondary tertiary care, Stroke, Translational research, Treated cancer,
- Publication type
- Journal Article MeSH
- Review MeSH
Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are: - Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects; - Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.
- Keywords
- Anthocyanidins, Anti-bacterial, Anti-cancer agents, Anti-inflammation, Anti-viral, COVID-19, Chalcones, Chemotherapy, Disease management, Drug-sensitizing effect, Flavanols, Flavanones, Flavones, Flavonoids, Flavonols, Health economy, Health policy, Immunotherapy, Isoflavonoids, Nano-carrier delivery, Phytochemicals, Predictive preventive personalized medicine (3PM/PPPM), Radiotherapy, Signalling pathways, Targeted therapy, Therapy efficacy, Therapy resistance,
- Publication type
- Journal Article MeSH
- Review MeSH
Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters-ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.
- Keywords
- MCF-7 cells, MDA-MB-231 cells, Rhus coriaria, angiogenesis, apoptosis, breast cancer, cancer stem cells, cell proliferation, epigenetics, mouse, rat, sumac,
- MeSH
- Apoptosis MeSH
- Cell Cycle MeSH
- Antineoplastic Agents, Phytogenic pharmacology MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Mice, Inbred BALB C MeSH
- Mice, Nude MeSH
- Mice MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Tumor Cells, Cultured MeSH
- Breast Neoplasms drug therapy metabolism pathology MeSH
- Rats, Sprague-Dawley MeSH
- Cell Proliferation MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Rhus chemistry MeSH
- Plant Extracts pharmacology MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antineoplastic Agents, Phytogenic MeSH
- MicroRNAs MeSH
- Biomarkers, Tumor MeSH
- Plant Extracts MeSH
Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds. Although genoprotective effects of phytochemicals have been well documented, there is an evident lack of articles which would systematically present the spectrum of anticancer effects by phytochemicals, plant extracts, and plant-derived diet applicable to stratified patient groups at the level of targeted primary (cancer development) and secondary (cancer progression and metastatic disease) prevention. Consequently, clinical implementation of knowledge accumulated in the area is still highly restricted. To stimulate coherent co-development of the dedicated plant bioactive compound investigation on one hand and comprehensive cancer preventive strategies on the other hand, the current paper highlights and deeply analyses relevant evidence available in the area. Key molecular mechanisms are presented to detail genoprotective and anticancer activities of plants and phytochemicals. Clinical implementation is discussed. Based on the presented evidence, advanced chemopreventive strategies in the context of 3P medicine are considered.
- Keywords
- Anti-inflammatory, Antibacterial, Anticancer, Antifungal, Antimutagenic effects, Antioxidant, Beneficiary effects, Biomarkers, Breast cancer, Chemoprevention, Colon cancer, Detoxification, Diet, Exogenous and endogenous agents, Genomic instability, Genoprotection, Genotoxicity, Glutaredoxins, Glutathione, Hydrogen peroxide, Nanoparticles, Nanotechnology, Oncology, Oxidative stress, Phytochemicals, Plant natural substances, Prebiotic, Preclinical and clinical study, Predictive Preventive Personalised Medicine (3PM, PPPM), Probiotic, ROS, Scavanger, Superoxide dismutase, Therapeutic potential, Thioredoxin, Tumour,
- Publication type
- Journal Article MeSH
- Review MeSH
Health-threatening consequences of carcinogen exposure are mediated via occurrence of electrophiles or reactive oxygen species. As a result, the accumulation of biomolecular damage leads to the cancer initiation, promotion or progression. Accordingly, there is an association between lifestyle factors including inappropriate diet or carcinogen formation during food processing, mainstream, second or third-hand tobacco smoke and other environmental or occupational carcinogens and malignant transformation. Nevertheless, increasing evidence supports the protective effects of naturally occurring phytochemicals against carcinogen exposure as well as carcinogenesis in general. Isolated phytochemicals or their mixtures present in the whole plant food demonstrate efficacy against malignancy induced by carcinogens widely spread in our environment. Phytochemicals also minimize the generation of carcinogenic substances during the processing of meat and meat products. Based on numerous data, selected phytochemicals or plant foods should be highly recommended to become a stable and regular part of the diet as the protectors against carcinogenesis.
- Keywords
- Antioxidant, Carcinogens, Chemoprevention, Detoxification, Dietary phytochemicals, Metabolic activation, Scavenging effect,
- MeSH
- Anticarcinogenic Agents pharmacology therapeutic use MeSH
- Phytochemicals pharmacology therapeutic use MeSH
- Carcinogenesis drug effects MeSH
- Carcinogens toxicity MeSH
- Humans MeSH
- Food adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Anticarcinogenic Agents MeSH
- Phytochemicals MeSH
- Carcinogens MeSH
Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters-ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.
- Keywords
- Cinnamomum zeylanicum, MCF-7 cells, MDA-MB-231 cells, apoptosis, cancer stem cells, cell proliferation, epigenetics, mammary carcinogenesis, mouse, preventive medicine, rat,
- MeSH
- Antineoplastic Agents, Phytogenic administration & dosage chemistry pharmacology MeSH
- Histones metabolism MeSH
- Rats MeSH
- Plant Bark chemistry MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- MicroRNAs genetics MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy genetics metabolism MeSH
- Oils, Volatile administration & dosage chemistry pharmacology MeSH
- Plant Oils administration & dosage chemistry pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Cinnamomum zeylanicum chemistry MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antineoplastic Agents, Phytogenic MeSH
- Histones MeSH
- MicroRNAs MeSH
- Oils, Volatile MeSH
- Plant Oils MeSH