Progressive relaxation training in patients with breast cancer receiving aromatase inhibitor therapy-randomized controlled trial.

BACKGROUND: Aromatase inhibitors have positive impacts on the disease-free life of patients with breast cancer. However, their side effects, especially arthralgia, may be experienced by many patients. This study sought to assess the efficacy of Progressive Relaxation Exercises on the prevalent side effects of Aromatase Inhibitors in patients with breast cancer. MATERIALS AND METHODS: This clinical trial was conducted with single-blind randomization at a physiotherapy department in a local hospital. Patients who received Aromatase Inhibitor were assigned at random to either the study or control group. The study group (n = 22) performed a Progressive Relaxation Exercises program four days a week for six weeks, while the control group (n = 22) received advice on relaxation for daily life. Data was collected before the intervention and after six weeks. The study's primary endpoint was the Brief Pain Inventory, which was used to measure pain severity. Secondary endpoints included assessments of quality of life and emotional status, which were measured using the Functional Assessment of Chronic Illness Therapy and Hospital Anxiety and Depression scales, respectively. RESULTS: The study group exhibited a significant reduction in Pain Severity (p = 0.001) and Pain Interference (p = 0.012) sub-scores. Reduction in Pain Severity (p<0.001) and Patient Pain Experience (p = 0.003) sub-scores was also noted between the groups. Quality of Life and Emotional Status showed no significant variation both within and between the groups (p>0.05). CONCLUSION: The study demonstrated that Progressive Relaxation Exercises caused a significant reduction in pain scores among Breast Cancer patients receiving Aromatase Inhibitors. While a decrease in pain during the 6-week period is valuable data, it is necessary to monitor the long-term effects of relaxation techniques.

Efficacy of the traditional Chinese medicine, Buyang Huanwu Decoction, at preventing taxane-induced peripheral neuropathy in breast cancer patients: A prospective, randomized, controlled study.

BACKGROUND: Buyang Huanwu Decoction (BYHWD) is a traditional Chinese prescription, originally derived from Yi Lin Gai Cuo during the Qing Dynasty. This study aimed to evaluate the efficacy and safety of BYHWD in the prevention of taxane-induced peripheral neuropathy (TIPN) in patients with breast cancer. METHODS: This single-center, statistician-blinded, parallel-group, simple randomized, no-treatment controlled study was conducted at the China-Japan Friendship Hospital in Beijing. Sixty breast cancer patients scheduled to receive nab-paclitaxel-based chemotherapy were randomly assigned to either the BYHWD group (N = 30) or the control group (N = 30) using simple randomization procedures. The data analysts were unaware of the treatment allocation. The primary efficacy endpoints were the incidence and severity of TIPN in the 2 groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and Patients' Neurotoxicity Questionnaire (PNQ). The secondary efficacy endpoint was the score of Functional Assessment of Cancer Therapy-Breast for both groups. The primary safety endpoints were routine blood test results and liver and renal functions. Both groups were subjected to 4 chemotherapy cycles. Efficacy and safety analyses were conducted on an intention-to-treat basis. RESULTS: The incidence of TIPN in the BYHWD group was 50.0%, which was lower than the 80.0% incidence in the control group (ß = -1.881 [95%CI -3.274, -.488]; P = .008, adjusted). The probability of TIPN in the BYHWD group was 15.2% of that in the control group, representing a significant reduction in incidence (odds ratio = .152, [95%CI .038, 0.614]; P = .008, adjusted). The CTCAE and PNQ grades of the BYHWD group were 1.527 and 1.495 points lower than those of the control group at the same cycle, respectively (CTCAE: ß = -1.527 [95%CI -2.522, -.533]; P = .003, adjusted; PNQ: ß = -1.495 [95%CI -2.501, -.489]; P = .004, adjusted, respectively). After treatment, the Functional Assessment of Cancer Therapy-Breast scores in the BYHWD group were significantly better than those in the control group (P = .003), especially in the physiological, functional, and additional concerns domains. CONCLUSION: Buyang Huanwu decoction (BYHWD) can effectively prevent TIPN and improve the quality of life in patients with breast cancer.

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells.

Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1ß, CYP1A1, and DNA POLß. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1ß and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLß protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.

A Standardized Extract of Petasites hybridus L., Containing the Active Ingredients Petasins, Acts as a Pro-Oxidant and Triggers Apoptosis through Elevating of NF-κB in a Highly Invasive Human Breast Cancer Cell Line.

BACKGROUND: Common butterbur (Petasites hybridus L.) is a traditional medicinal plant with numerous therapeutic properties among which is its recently uncovered anti-tumor activity. The present study aims to examine the activity of a standardized Bulgarian Petasites hybridus L. root extract, containing the active ingredients petasins, on the human breast cancer cell line MDA-MB-231 and non-cancerous MCF-10A cells. Specifically, we examined cell death, oxidative stress, and nuclear factor kappa-B (NF-κB) signaling. METHODS: A standardized butterbur powdered extract containing a minimum of 15% petasins was used. A lipophilic extract was obtained from subterranean portion of the plant of Bulgarian populations of Petasites hybridus using liquid-liquid extraction after completely removing pyrrolizidine alkaloids. The induction of apoptosis and necrosis was analyzed by flow cytometry, and oxidative stress biomarkers and NF-κB were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Petasites hybridus L. root extract triggered apoptosis in a cancer-specific fashion and induced a moderate oxidative stress characterized by diminished glutathione (GSH) levels and elevated malondialdehyde (MDA) levels in MDA-MB-231 72 h after treatment. NF-κB levels were higher in cancer cells after treatment with IC50 and IC75 doses, this suggested that the NF-κB pathway was activated in response to oxidative stress leading to the induction of apoptosis. MCF-10A cells were affected to a lesser extent by the Petasites hybridus extract, and the adaptive response of their antioxidant defense system halted oxidative stress. CONCLUSIONS: Overall, these results indicate that Petasites hybridus L. root extract selectively acts as a pro-oxidant in breast cancer cells and thus represents a potential therapeutic option for cancer treatment with fewer side effects.

Single Nucleotide Polymorphism Directed Antiemetic Treatment in Women With Breast Cancer Treated With Neo- or Adjuvant Chemotherapy: A Randomised Multicentre Phase II Study. (EudraCT: 2015-000658-39).

BACKGROUND/AIM: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment. PATIENTS AND METHODS: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment. RESULTS: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment. CONCLUSION: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

A comparative study of the efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in gynecomastia: A retrospective cohort study.

To compare the clinical efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in patients with gynecomastia and discuss the safety of the two treatments. We retrospectively analysed the clinical data of 388 male patients with gynecomastia who were treated in the Outpatient Clinic of our hospital between January 2010 and December 2020. There were 103 patients in the tamoxifen (TAM) group and 103 patients in the Chinese patented medicine group. There were 182 patients in the observation group (non-medication group; age range, 11-75 years; average age, 33.1 years). The natural outcomes were compared between the observation and two medication groups under the same conditions. Disease progression was compared between the observation and two medication groups over the same treatment duration to confirm the efficacy of the medication treatments. Patients with clinical grade 2 gynecomastia accounted for the highest proportion of patients in the TAM group. The percentage of patients with clinical grade 2 gynecomastia was comparable in the Chinese patented medicine and observation groups. The percentage of patients with clinical grades 1 and 3 gynecomastia was the lowest in the TAM group and comparable among the three groups (p = 0.014). The TAM group had the largest number of patients achieving breast shrinkage, and therefore had the best efficacy (p = 0.000). Among the three groups, the surgery rate was the highest in the observation group (p = 0.000). Patients with the greatest glandular tissue thickness achieved better outcomes after medication treatment (p = 0.000). Patients with a higher clinical grade also had a higher surgery rate (p = 0.000). Some patients from the TAM and Chinese patented medicine groups had side effects. TAM results in better outcomes than Chinese patented medicine in gynecomastia patients. The surgery rate is the highest in the observation group. In addition, among some patients with a greater glandular tissue thickness, the higher the clinical grade is, the higher the surgery rate is. Both TAM and Chinese patented medicine cause some side effects and should be used with caution along with continuous follow-up evaluation of patients receiving either treatment.

Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort.

BACKGROUND: Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited. OBJECTIVES: This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status. METHODS: This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS: The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer. CONCLUSIONS: Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

Effects of Acupuncture on Breast Cancer Patients Taking Aromatase Inhibitors.

Although acupuncture has been used in clinical practice for thousands of years, it remains a controversial treatment option to help alleviate pain in cancer patients. In this study, we analyzed published material on randomized trials of acupuncture from MEDLINE published up until July 31, 2018, to assess its effects on pain experienced by cancer patients. Revman 5.0 software was used to conduct meta-analysis with pain score as the index. The results of nine randomized controlled trials involving 592 patients were analyzed and showed that acupuncture can relieve the pain caused by aromatase inhibitors. Weighted mean difference of worst pain and pain severity was -3.03, 95% CI (-3.90,-2.16) and -2.69, 95% CI (-4.08,-1.30), respectively (P < 0.01). This led us to conclude that acupuncture has pain relieving effects against pain caused by aromatase inhibitors.

Coffee and tea consumption, patient-reported, and clinical outcomes in a longitudinal study of patients with breast cancer.

BACKGROUND: Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient-reported outcomes (PROs) and clinical outcomes among survivors of BC. METHODS: The authors included survivors of stage I-III BC enrolled in the CANTO cohort (NCT01993498) that provided post-treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group-based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes. RESULTS: Among 3788 patients, the authors identified four stable patterns of consumption: "Low" (25.8%), "Moderate" (37.6%), "High" (25.3%), and "Very high" (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the "Very high" group (vs. "Low"), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups. CONCLUSIONS: Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes.

Positive association between dietary exposure to polybrominated diphenyl ethers and breast cancer risk in the French E3N cohort: The role of vegetable oil consumption.

Exposure to endocrine-disrupting chemicals, like Polybrominated diphenyl ethers (PBDEs), is suspected of playing a role in the occurrence of breast cancer. Moreover, there is growing evidence that food chemical contaminants, especially lipophilic ones such as PBDEs, could interact with different components of the diet. The objective of the present study was to assess the association between dietary intake of PBDEs and breast cancer risk in the French E3N cohort study, and to investigate the potential modification of this association by vegetable oil consumption. The study included 67879 women. Intakes of eight PBDEs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire, and food contamination levels measured by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES). Cox proportional hazards models were used to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) for the association between total PBDEs dietary intake and breast cancer risk. Interaction measures for vegetable oil consumption were estimated on both additive and multiplicative scales. The women were followed for a maximum of 21.4 years, and 5 686 developed an incident breast cancer. A positive linear trend was highlighted between dietary intake of PBDEs in quintile groups and breast cancer risk, borderline with statistical significance (p-trend = 0.06, HRQ5vsQ1 and 95% CI: 1.09 [0.99;1.20]). Interaction measures for vegetable oil consumption were significant in both additive and multiplicative scales. Higher effect sizes of the association were highlighted in high consumers of vegetable oil, i.e. ≥4.6 g/day (HRQ5vsQ1 and 95% CI: 1.23 [1.08; 1.40]), and almost no effect were found in low consumers (HRQ5vsQ1 and 95% CI: 0.97 [0.86; 1.10]). Highlighting such interactions between nutrients and chemicals is crucial to develop efficient dietary recommendations to limit the negative health effects associated with exposure to food chemical contaminants.

Changes in Vertebral Marrow Fat Fraction Using 3D Fat Analysis & Calculation Technique Imaging Sequence in Aromatase Inhibitor-Treated Breast Cancer Women.

Aromatase inhibitor (AI) is a cornerstone drug for postmenopausal women with estrogen receptor-positive early-stage breast cancer. Fat-bone interactions within the bone marrow milieu are growing areas of scientific interest. Although AI treatment could lead to deterioration of the skeleton, the association between AI medication and subsequent marrow adiposity remains elusive. A total of 40 postmenopausal, early-staged, and hormone receptor-positive breast cancer patients who underwent treatment with adjuvant AIs and 40 matched controls were included. Marrow proton density fat fraction (PDFF) at the L1-L4 vertebral bodies using 3D Fat Analysis & Calculation Technique imaging (FACT) sequence at 3.0T, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and serum bone turnover biomarkers were determined at baseline and at 6 and 12 months. We found that, in comparison to baseline, an increase of type I collagen cross-linked telopeptide was detected at 12 months (P <0.05). From baseline to 12 months, the PDFF measured using FACT was greatly increased. At 12 months, the median percent change of PDFF (4.9% vs. 0.9%, P <0.05) was significantly different between the AI treatments and controls. The same trend was observed for the marrow PDFF at 6 months relative to the respective values at baseline. Although BMD values were significantly reduced after 12 months in AI-treated women, changes in BMD vs. baseline condition were not significantly different between the AI-treated and control groups [Δ BMD -1.6% to -1.8% vs. -0.3% to -0.6%, respectively, P > 0.05]. In the AI-treated group, Δ PDFF was associated with Δ BMD at the lumbar spine (r = -0.585, P < 0.001), but not in the controls. Taken together, over a 12-month period, spinal marrow fat content assessed with FACT sequence significantly increased in postmenopausal women with hormone-receptor-positive breast cancer receiving AI treatment.

Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach.

Turmeric is one of the most used herbal supplements among cancer patients. It reportedly modulates the function of CYP450 enzymes and drug transporters. This study investigates the effect of turmeric on the pharmacokinetics of paclitaxel in breast cancer patients. This is a prospective longitudinal study with 60 breast cancer patients on treatment with single-agent paclitaxel and turmeric. The patients were followed up for two consecutive chemotherapy cycles, and their blood samples were collected, first without turmeric (first cycle) and the next after a 21-day concomitant administration of 2 g/day turmeric (second cycle). Plasma samples were quantified for paclitaxel concentration using High Performance Liquid Chromatograph with UV detector (HPLC-UV) method. The sparse concentration-time data of paclitaxel were subjected to population pharmacokinetic modeling, and then noncompartmental analysis (NCA) was performed on the simulated data to estimate the pharmacokinetic parameters of paclitaxel, before and after turmeric supplementation, for comparisons. The population pharmacokinetic parameters of paclitaxel differed from before to after turmeric supplementation. NCA of simulated concentration-time profiles showed a statistically significant reduction of 7.7% and 12.1% in AUCinf and Cmax, respectively. Given the small magnitude of the changes in pharmacokinetic parameters, the observed changes are not clinically relevant. Thereby, turmeric at the recommended dose can be combined safely with paclitaxel.

Breast cancer therapy and bone.

Breast cancer is the most common cancer in women and the leading cause of cancer-associated mortality. The estrogen deprivation associated with therapies used to treat this disease may result in significant loss of bone density and a consequent increase in fracture risk. Anti-resorptive osteoporosis therapies (bisphosphonates and the inhibitor of receptor activator of nuclear factor-κB ligand [RANKL] denosumab) play an important role in the mitigation of cancer therapy-induced bone loss (CTIBL), and may function as adjuvant therapy in moderate to high-risk breast cancer to prevent disease recurrence. Various international guidelines have delineated treatment thresholds based on both bone density assessment and clinical risk factors for CTIBL. The role of these bone-targeted therapies as adjuvant anti-cancer treatment is evolving. Currently, evidence supports the use of the bisphosphonates, zoledronic acid and clodronate, in this setting. Unfortunately, a focus on bone health in women with breast cancer is often not prioritized, leaving this group vulnerable to significant bone loss and subsequent fracture.

The Influence of Supplementation with Zinc in Micro and Nano Forms on the Metabolism of Fatty Acids in Livers of Rats with Breast Cancer.

The aim of this study was to investigate the effect of zinc supplementation (in the form of nano or microparticles) on the profile and metabolism of fatty acids in the liver microsomes of rats with induced breast cancer. The activity of desaturases (Δ5, Δ6, Δ9) and the level of cholesterol and its oxidized derivatives were measured. The aim of this study was also to determine the effect of various forms of zinc supplements on rats that were on 5-, 12- and 15-hydroxyeicosatetraenoic (5-, 12- and 15-HETE) and hydroxyoctadecadienoic (HODE) acids, and the level of prostaglandin E2 (PGE2). Female Spraque-Dawley rats (n = 24) were divided into 2 groups that were supplemented with zinc in the micro form (342 nm) or nano form (99 nm) particles, respectively, and a group with a standard diet (control group). All animals received 7,12-dimethylbenz[a]anthracene twice for the induction of breast cancer. Dietary nano-Zn supplementation increased vaccenic acid content (p = 0.032) and decreased Δ6-desaturase activity (p = 0.006), whereas micro-Zn increased cholesterol (p = 0.006), ∑COPs (total cholesterol-oxidation products) (p = 0.019) and PGE2 (p = 0.028) content. Dietary enrichment with Zn microparticles resulted in lower concentrations of the metabolites 15-, 12- and 5-HETE and HODE. Our study indicates that the effect of zinc supplementation on the metabolism of fatty acids in the liver microsomes under neoplastic conditions depends on the form in which it is administered.

In-silico HMG-CoA reductase-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.

OBJECTIVES: Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin. METHODS: Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects. KEY FINDINGS: Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-ß-ß-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs. CONCLUSION: Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.

Tumorigenic risk of Angelica sinensis on ER-positive breast cancer growth through ER-induced stemness in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Angelica sinensis is widely used in traditional Chinese Medicine for relieving gynecological discomforts among the women population. However, its hormone-like effects have raised great attention on whether it is appropriate to use in breast cancer (BC) patients. Hence, this study aimed to investigate the tumorigenic effect of aqueous root extract of Angelica sinensis (AS) on estrogen receptor (ER)-positive BC growth through ER-induced stemness in-vitro and in-vivo. MATERIALS AND METHODS: The chemical composition of the AS was characterized by HPLC. Cell viability was detected by MTS assay. The in-vivo effect of AS was investigated by xenograft model, immunohistochemistry, histology, Western blot, and self-renewal ability assay. Target verification was used by shRNA construction and transfection. Mammosphere formation assay was performed by flow cytometry. RESULTS: AS significantly promoted the proliferation of MCF-7 cells and inhibited the growth of MDA-MB-231 cells. AS significantly induced tumor growth (2.5 mg/kg) in xenograft models and however tamoxifen treatment significantly suppressed the AS-induced tumor growth. AS induced ERα expression in both in-vivo and in-vitro and promoted cancer stem cell activity in ER-positive BC. CONCLUSION: AS shows the tumorigenic potential on ER-positive BC growth through ERα induced stemness, suggesting that the usage of AS is not recommended for BC in terms of safety measures.

Zinc Affects Cholesterol Oxidation Products and Fatty Acids Composition in Rats' Serum.

The purpose of this work was to evaluate the effect of the nanosized or microsized zinc (Zn) particles on fatty acid profile, enzyme activity and the level of cholesterol, squalene and oxysterols in rats with breast cancer. Rats (female, n = 24) were divided into the following groups: control, and two test groups, whose diets were enriched with either Zn microparticles (342 nm) or Zn nanoparticles (99 nm). All rats were treated twice with the carcinogenic agent; 7,12-dimethylbenz[a]anthracene. In rats whose diet was enriched with zinc (especially in the form of nanoparticles), the number and sizes of tumors were lower. Diet supplementation also significantly reduced the cholesterol (p = 0.027) and COPs (cholesterol oxidation products) levels (p = 0.011) in rats serum. Enriching the diet with Zn microparticles decreased the Δ6-desaturase activity (p < 0.001). Zn influences fatty acids' profile in rats' serum as well as inhibiting desaturating enzymes. A reduced amount of pro-inflammatory arachidonic acid derivatives may be the expected effect.

LC-MS characterized methanolic extract of zanthoxylum armatum possess anti-breast cancer activity through Nrf2-Keap1 pathway: An in-silico, in-vitro and in-vivo evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum armatum DC (Rutaceae) containing flavonoids, alkaloids, coumarins, lignans, amides and terpenoid is well-known for its curative properties against various ailments including cancer. In the current research, phytochemicals present in the methanolic extract of Zanthoxylum armatum bark (MeZb) were characterized by LC-MS/MS analysis and chemotherapeutic potential of this extract was determined on DMBA-induced female Sprague Dawley rats. MATERIALS AND METHODS: A simple and fast high-performance liquid chromatography-mass spectroscopy (LC-MS/MS) of MeZb was established followed by in-vitro antioxidant assays. This was followed by in-silico docking analysis as well as cytotoxicity assessment. Successively in-vivo study of MeZb was performed in DMBA-induced Sprague Dawley rats possessing breast cancer along with detailed molecular biology studies involving immunofluorescence, RT-qPCR and Western blot analysis. RESULTS: LC-MS/MS investigation revealed the presence of compounds belonging to flavonoid, alkaloid and glycoside groups. MeZb revealed potential antioxidant activity in in-vitro antioxidant assays and strong binding energy of identified compounds was seen from the in-silico study with both HO1 and Keap1 receptor. Furthermore, the antioxidant action of MeZb was proven from the in-vivo analysis of antioxidant marker enzymes (lipid peroxidation, enzymic and non-enzymic antioxidants). This study also revealed upregulation of protective Nrf-2 following downregulation of Keap1 after MeZb treatment with respect to untreated cancerous rats. CONCLUSION: These results exhibited anti-breast-cancer potential of MeZb through Nrf2-Keap1 pathway which may be due to the flavonoids, alkaloids and glycosides present in it.