RESUMO
Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related mortality. Existing treatment strategies for gastric cancer often present numerous side effects. Consequently, recent studies have shifted toward devising new treatments grounded in safer natural substances. α-Pinene, a natural terpene found in the essential oils of various plants, such as Lavender angustifolia and Satureja myrtifolia, displays antioxidant, antibiotic, and anticancer properties. Yet, its impact on gastric cancer remains unexplored. This research assessed the effects of α-pinene in vitro using a human gastric adenocarcinoma cell-line (AGS) human gastric cancer cells and in vivo via a xenograft mouse model. The survival rate of AGS cells treated with α-pinene was notably lower than that of the control group, as revealed by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. This decline in cell viability was linked to apoptosis, as verified by 4',6-diamidino-2-phenylindole and annexin V/propidium iodide staining. The α-pinene-treated group exhibited elevated cleaved-poly (ADP-ribose) polymerase and B cell lymphoma 2 (Bcl-2)-associated X (Bax) levels and reduced Bcl-2 levels compared with the control levels. Moreover, α-pinene triggered the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 within the mitogen-activated protein kinase (MAPK) pathway. In the xenograft mouse model, α-pinene induced apoptosis through the MAPK pathway, devoid of toxicity. These findings position α-pinene as a promising natural therapeutic for gastric cancer.
Assuntos
Monoterpenos Bicíclicos , Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Apoptose , MAP Quinases Reguladas por Sinal Extracelular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proliferação de CélulasRESUMO
Partial nephrectomy (PN) is the gold standard for the resection of amenable small renal masses. Some surgeons have adopted tumor enucleation (TE) over the standard margin PN (SPN) technique based on preservation of healthy renal parenchyma by following the tumor pseudocapsule. However, TE may also confer additional advantages due to avoidance of sharp incision including reduction in perioperative and bleeding complications. Therefore, we evaluated the rate of pseudoaneurysms and other complications following TE vs. SPN. A retrospective cohort study of patients undergoing PN (TE and SPN) between 2008 and 2020 was conducted. Baseline characteristics were compared between the TE and SPN cohorts with univariable and multivariable logistic regression models. A total of 534 patients were included, 195 (36.5%) receiving TE and 339 (63.5%) SPN. There were no differences in baseline patient demographics. There was no difference in RENAL nephrometry scores between the two groups (p = 0.47). TE had lower rates of postoperative complications (11.3 vs. 21.5%, p = 0.002). TE had less bleeding complications (2.1 vs. 8.0%, p = 0.002) with no pseudoaneurysm events following TE compared to 12 following SPN (0.0 vs. 3.5%, p = 0.008). Need for interventional radiology largely reflected pseudoaneurysm differences (0 (0.0%) TE vs. 13 (3.8%) SPN, p = 0.006. Readmission occurred less often after TE vs. SPN (4.1 vs. 8.3%, p = 0.07). Patients receiving TE experienced no clinically significant pseudoaneurysm formation and were less likely to have any bleeding complication or major complication postoperatively. TE may be preferred when minimizing morbidity aligns with patient selection and preferences.
Assuntos
Falso Aneurisma , Neoplasias , Procedimentos Cirúrgicos Robóticos , Humanos , Falso Aneurisma/epidemiologia , Falso Aneurisma/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Nefrectomia/efeitos adversosRESUMO
This study sought to determine the anticancer effect of kaempferol, a glycone-type flavonoid glycoside with various pharmacological benefits, on human oral cancer MC-3 cells. In vitro studies comprised a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V and propidium iodide staining, western blotting analysis, and acridine orange staining, while the in vivo studies entailed a xenograft model, hematoxylin and eosin staining, and TdT-mediated dUTP-biotin nick end labelling. In vitro, kaempferol reduced the rate of survival of MC-3 cells, mediated intrinsic apoptosis, increased the number of acidic vesicular organelles, and altered the expression of autophagy-related proteins. Further, treatment with the autophagy inhibitors revealed that the induced autophagy had a cytoprotective effect on apoptosis in kaempferol-treated MC-3 cells. Kaempferol also decreased the expression of phosphorylated extracellular signal-regulated kinase and increased that of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated p38 kinase in MC-3 cells, suggesting the occurrence of mitogen-activated protein kinase-mediated apoptosis and JNK-mediated autophagy. In vivo, kaempferol reduced tumor growth inducing apoptosis and autophagy. These results showed that kaempferol has the potential use as an adjunctive agent in treating oral cancer.
RESUMO
Platycodin D (PD) is the main component of triterpene saponins found in Platycodi radix. In this study, we observed a decrease in cell viability, an increase in apoptotic bodies, and an increase in the rate of apoptosis. Also, we observed an increase in cleaved PARP and Bax, a decrease in Bcl-2, and p-ERK, and an increase in p-p38 and p-JNK. Furthermore, a change in cell viability and the expression of p-p38, Bax, and Bcl-2 using the p38 inhibitor revealed a decrease in p-p38 and Bax and an increase in Bcl-2 in the inhibitor treatment group. In addition, we observed an increase in vacuole formation through morphological changes and an increase in acidic vesicular organelles (AVOs). We also observed an increase in the expression of beclin 1, LC 3-I, and -II. There was no significant decrease in cell viability in the group treated with 3-MA, but a decrease in cell viability was noted in the group treated with HCQ. HCQ treatment resulted in an increase in Bax and a decrease in Bcl-2. These findings reveal that in HT-29 colon cancer cells, PD induces apoptosis through the MAPK pathway, thereby exerting anticancer effects. Moreover, autophagy caused by PD inhibits apoptosis by protecting the cells.
Assuntos
Neoplasias do Colo , Saponinas , Triterpenos , Humanos , Proteína X Associada a bcl-2 , Saponinas/farmacologia , Triterpenos/farmacologia , Apoptose , Autofagia , Neoplasias do Colo/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2RESUMO
OBJECTIVES: This study aims to evaluate the efficacy and toxicity of radiotherapy (RT) to oligoprogressive metastatic non-small cell lung cancer (NSCLC). METHODS: This is a retrospective analysis of 23 patients with metastatic NSCLC on maintenance systemic therapy, developed oligoprogression (1 to 5 sites), and all oligoprogressive sites amenable to and treated with RT. The primary endpoints included progression-free survival (PFS) and median time to start next-line therapy (MTT). Kaplan-Meier survival analysis and log-rank testing were performed using R-Studio software. RESULTS: Twenty-three patients met the inclusion criteria. The median overall survival for the entire cohort was 31.3 months (interquartile range [IQR]: 17.86 to 45.4). The median event-free survival for the entire cohort was 8.3 months (IQR: 2.7 to 12). Patients with no prior radiation had longer median event-free survival of 11.9 months (IQR: 8.4 to 18.2) compared with patients with a history of prior radiation at 4.1 months (IQR: 2.7 to 12; P = 0.041). The local control rate for the treated lesions was 97.5%. At 12 months follow-up, 6 (43%) of 14 living patients maintained systemic therapy without initiating next-line therapy. The median PFS for the entire cohort was 8.4 months (IQR: 4.1 to 17.5). Patients who did not receive prior radiation had longer median PFS of 11.9 months (IQR: 8.4 to 18.2) compared with patients who received prior radiation 6.2 months (IQR: 2.7 to 8.5; P = 0.018). Two patients (9%) had grade 3 chronic toxicity related to RT and were medically managed. CONCLUSION: We identified that in patients with oligoprogressive metastatic NSCLC, targeted RT to all progressive sites yielded high LC and favorable rates of PFS and MTT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Intervalo Livre de ProgressãoRESUMO
Climate change, driven by increased greenhouse gas emissions, is a pressing environmental issue worldwide. Flooded rice paddy soils are a predominant source of methane (CH4) emissions, accounting for approximately 11 % of global emissions. Factors such as rice (Oryza sativa L.) cultivar, transplanting date, water management, and soil characteristics significantly influence these emissions. This study aimed to evaluate the CH4 emissions from rice paddies in relation to the cultivar and transplanting date. The experiment included two rice cultivars (an early-maturing cultivar, Unkwang, and a medium-late-maturing cultivar, Samkwang) and four transplanting dates (Times 1-4). In the present study, CH4 emissions were higher with earlier transplanting dates and decreased significantly with delayed transplanting. Weather conditions, such as cumulative mean air temperature, cumulative soil temperature, and total sunshine hours, were positively correlated with total CH4 emissions. The recommended regional transplanting date (Time 3) resulted in the highest rice grain yields for both cultivars. However, the earlier transplanting dates (Time 1 and Time 2) were more effective in improving plant growth characteristics such as rice straw weight, root biomass weight, and chlorophyll content. A significant positive correlation was observed between the root biomass weight of the rice and CH4 emissions in both cultivars, implying that an increase in root biomass weight led to an increase in CH4 emissions. Consequently, adhering to the advised regional transplanting dates is the most sensible approach for transplanting rice seedlings. This ensured lower CH4 emissions without compromising rice productivity or quality for both cultivars. Further research should focus on identifying the most appropriate rice-transplanting dates and management practices to effectively reduce CH4 emissions without compromising rice production.
Assuntos
Gases de Efeito Estufa , Oryza , Agricultura/métodos , Metano/análise , Solo , Gases de Efeito Estufa/análise , Óxido NitrosoRESUMO
BACKGROUND/AIM: The toxic side effects of therapies against breast cancer can affect the quality of life of patients, necessitating the use of naturally-derived therapeutics. Here, we investigated the effects of Dendropanax morbiferus H. Lév. leaf (DPL) extract on breast cancer cells in vitro and in vivo to assess its anticancer potential. MATERIALS AND METHODS: MDA-MB-231 breast cancer cells were treated with DPL, and the in vitro effect of DPL on the cells was evaluated through an MTT assay, DAPI staining, annexin V/propidium iodide double staining, and western blotting. The in vivo effects of DPL were measured through the MDA-MB-231 tumor xenograft mouse model. A TUNEL assay and immunohistochemistry were used to determine the extent of apoptosis and p-p38 expression in tumor tissues, respectively. RESULTS: DPL treatment significantly suppressed cell viability in a concentration-dependent manner. Furthermore, DPL treatment resulted in increased apoptotic body formation, apoptosis rate, cleaved poly (ADP-ribose) polymerase and B-cell lymphoma 2 (Bcl-2)-associated X protein levels, phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins, and decreased Bcl-2 levels. In addition, the antitumor effect in vivo was confirmed through the xenograft model, where decreased tumor volume and weight following DPL administration were observed. Further, apoptosis and increased p-p38 levels in tumor tissues were observed, and no pathological abnormalities were found in the liver or kidney. CONCLUSION: DPL inhibits proliferation through MAPK-mediated apoptosis in breast cancer cells and tumors, suggesting the potential of DPL as a natural therapeutic agent for breast cancer.
Assuntos
Neoplasias da Mama , Proteínas Quinases Ativadas por Mitógeno , Humanos , Animais , Camundongos , Feminino , Qualidade de Vida , Proliferação de Células , Neoplasias da Mama/patologia , Apoptose , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2 , Linhagem Celular TumoralRESUMO
Background: The rise in telecommuting or non-face-to-face work owing to the coronavirus disease 2019 pandemic has fueled conversations regarding the "right to disconnect." Although evidence suggests that receiving work-related communications through telecommunication devices outside of work hours may lead to various symptoms and illnesses, limited research has been undertaken on these symptoms. This study therefore aims to investigate the correlation between receiving work communications through telecommunication devices after work hours and the occurrence of work-related headaches and eyestrain in full-time, non-shift white-collar workers. Methods: This study used data from the 6th Korean Working Conditions Survey. The frequency of using telecommunication devices for work purposes outside of working hours was divided into five categories: "Every day," "Several times a week," "Several times a month," "Rarely," and "Never." Work-related headaches and eyestrain were categorized based on a "yes" or "no" response to the survey questions. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using SPSS 27.0. Results: After adjusting for sex, age, income level, education, occupation, workplace size, work hours, and sleep disorders, the odds ratio (OR) of work-related headaches and eyestrain based on frequency of telecommunication device usage were as follows: "rarely" (OR: 1.292; 95% confidence interval [CI]: 1.111-1.503), "several times a month" (OR: 1.551; 95% CI: 1.249-1.926), "several times a week" (OR: 1.474; 95% CI: 1.217-1.784), and "every day" (OR: 1.548; 95% CI: 1.321-1.813). Conclusions: Employees who use telecommunication devices for work after regular hours are more susceptible to experiencing work-related headaches and eyestrain compared to those who do not. However, there is a dearth of research examining the physical and mental health impacts of using telecommunication devices for after-hours work. Furthermore, the existing preventative measures in Korea are insufficient. Consequently, it is imperative to develop effective measures and conduct additional research to address this issue.
RESUMO
Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.
Assuntos
Apoptose , Neoplasias Bucais , Humanos , Serina-Treonina Quinases TOR/metabolismo , Flavonoides/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Autofagia , Linhagem Celular Tumoral , Neoplasias Bucais/tratamento farmacológicoRESUMO
BACKGROUND: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. METHODOLOGY: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. RESULTS: An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. CONCLUSION: Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.
Assuntos
Linfopenia , Neoplasias , Feminino , Humanos , Linfopenia/etiologia , Linfopenia/prevenção & controle , Linfócitos/patologia , Planejamento da Radioterapia Assistida por Computador , Neoplasias/radioterapia , ImunoterapiaRESUMO
Background: Work is an inseparable element of a person's life, and violence in the workplace has various effects on individual workers and companies. While most studies have focused on specific industries, very few studies have investigated the influence of workplace violence by co-workers. Therefore, this study aimed to evaluate the association between workplace violence and work-related depression/anxiety in various occupations by differentiating the perpetrators of violence as co-workers and clients. Methods: This study was conducted based on data from the 4th and 5th Korean Working Conditions Surveys (KWCS). The experience of workplace violence was classified in terms of the perpetrator: workplace violence by co-workers and that by clients. Work-related depression and anxiety were assessed using questions about health problems related to depression and anxiety and whether the problems were related to work. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using the SPSS 26.0. Results: After adjusting for sociodemographic characteristics (age, education, income, subjective health status) and occupational characteristics (occupation, weekly working hours, type of employment, size of workplace, and shift work), male workers with experience of workplace violence by co-workers were found to be at a higher risk of work-related depression/anxiety (odds ratio [OR], 11.52; 95% confidence interval [CI], 8.65-15.36). The same was confirmed for female workers (OR, 10.89; 95% CI, 7.90-15.02). Conclusions: Employees who experienced workplace violence from co-workers were found to be more vulnerable to work-related depression/anxiety. Continuous contact between the victim and the perpetrator may occur, and the possibility of a secondary assault can frighten the victim. Appropriate prevention and intervention measures that focus on the perpetrators of violence are needed.
RESUMO
A quick, accurate and cost-effective method for estimating total soil carbon is necessary for monitoring its levels due to its environmentally and agronomically irreplaceable importance. There are several impediments to both laboratory analysis and spectroscopic sensor technology because the former is both expensive and time-consuming whereas the initial cost of the latter is too high for farmers to afford. RGB photography obtained from digital cameras could be used to quickly and cheaply estimate the total carbon (TC) content of the soil. In this study, we developed models to predict soil TC contents across different cropland types including paddy, upland and orchard fields as well as the TC content of the soil combined from all the aforementioned cropland types on a regional scale. Soil colour measurements were made on samples from the Chungcheongnam-do province of South Korea. The soil TC content ranged from 0.045% to 6.297%. Modelling was performed using multiple linear regression considering the soil moisture levels and illuminance. The best soil TC prediction model came from the upland soil and gave training and validation r2 values of 0.536 and 0.591 with RMSE values of 0.712% and 0.441%, respectively. However, the most accurate equation is the one that produces the lowest RMSE value. Hence, although the model for the upland soil was the most stable of all, the paddy soil model which gave training and validation r2 values of 0.531 and 0.554 with RMSE values of 0.240% and 0.199%, respectively, was selected as the best soil TC prediction equation of all due to its comparatively high r2 value and the lowest RMSE of all equations.
Assuntos
Carbono , Solo , Agricultura/métodos , Carbono/análise , Produtos Agrícolas , Fotografação , Solo/químicaRESUMO
Chrysin is known to exert anti-inflammatory, antioxidant, and anticancer effects. The aim of this study was to investigate the anticancer effects of chrysin in the human melanoma cells A375SM and A375P. The results obtained demonstrated successful inhibition of the viability of these cells by inducing apoptosis and autophagy. This was confirmed by the level of apoptosis-related proteins: Bax and cleaved poly (ADP-ribose) polymerase both increased, and Bcl-2 decreased. Moreover, levels of LC3 and Beclin 1, both autophagy-related proteins, increased in chrysin-treated cells. Autophagic vacuoles and acidic vesicular organelles were observed in both cell lines treated with chrysin. Both cell lines showed different tendencies during chrysin-induced autophagy inhibition, indicating that autophagy has different effects depending on the cell type. In A375SM, the early autophagy inhibitor 3-methyladenine (3-MA) was unaffected; however, cell viability decreased when treated with the late autophagy inhibitor hydroxychloroquine (HCQ). In contrast, HCQ was unaffected in A375P; however, cell viability increased when treated with 3-MA. Chrysin also decreased the phosphorylation of mTOR/S6K pathway proteins, indicating that this pathway is involved in chrysin-induced apoptosis and autophagy for A375SM and A375P. However, studies to elucidate the mechanisms of autophagy and the action of chrysin in vivo are still needed.
RESUMO
Tenebrio molitor larvae, as known as edible insects, has advantages of being rich in protein, and has been recognized as a suitable alternate protein source for broiler and pig feed. Moreover, given their ability to biodegrade polystyrene, a major pollutant, Tenebrio molitor larvae has been proposed as an innovative solution to environmental problems. In the present study, we investigated the toxicity of Tenebrio molitor larvae powder (TMlp) ingested with expanded-polystyrene (W/ eps) through in vitro and in vivo experiments. The objective of this study was to determine whether TMlp W/ eps can be applied as livestock alternative protein source. For in vitro experiments, cytotoxicity test was performed to investigate the effects of TMlp-extract on the viability of estrogen-dependent MCF-7 cells. The possibility of estrogen response was investigated in two groups: Expanded-polystyrene-fed (W/ eps) TMlp group and without expanded-polystyrene-fed (W/o eps) TMlp group. For in vivo experiments, The male Sprague-Dawley rats were divided based on the dosage of TMlp administered and oral administration was performed to every day for 5 weeks. A toxicological assessments were performed, which included clinical signs, food consumption, body and organ weights, hematology, serum chemistry, and hematoxylin and eosin staining of liver and kidney. There were no specific adverse effect of TMlp W/ eps-related findings under the experimental conditions of this study, but further studies on both sexes and animal species differences should be investigated. In conclusion, TMlp W/ eps was considered non-toxic and observed to be applicable as an alternative protein source for livestock feed.
RESUMO
Myricetin, a natural flavonoid present in berries, nuts, and green tea, is well-known for its anticancer properties. Even though several previous studies have reported the anticancer effects induced by myricetin, these effects have not yet been confirmed in the adenocarcinoma gastric cell line (AGS). Moreover, the exact mechanisms of myricetin-induced apoptosis and autophagy have not been clearly identified either. Therefore, in this study, we aimed to examine the role of myricetin in inducing apoptosis and autophagy in AGS gastric cancer cells. First, the survival rate of AGS gastric cancer cells was assessed using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) cell viability assay. Thereafter, the rate of apoptosis was analyzed using4',6-diamidino-2-phenylindole (DAPI) staining as well as annexin V and propidium iodide (PI) staining, and the expression of the proteins associated with apoptosis, PI3K/Akt/mTOR pathway, and autophagy was examined by western blotting. We observed that myricetin reduced the survival rate of AGS gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway, thereby inducing apoptosis and autophagy. Similar results were also obtained in vivo, and tumor growth was inhibited. Therefore, in the AGS gastric cancer cells, myricetin seems to inhibit the PI3K/Akt/mTOR pathway, which in turn leads to apoptosis in vitroand in vivo, cell-protective autophagy, as well as inhibition of cancer cell proliferation. These results indicate the potential of myricetin as a natural anticancer agent.
RESUMO
Myricetin, a flavonoid found in fruits and vegetables, is known to have antioxidant and anticancer effects. However, the anticancer effects of myricetin on SKBR3 human breast cancer cells have not been elucidated. In the present study, the anticancer effects of myricetin were confirmed in human breast cancer SKBR3 cells. As the concentration of myricetin increased, the cell viability decreased. DAPI (4',6diamidino2phenylindole) and Annexin V/PI staining also revealed a significant increase in apoptotic bodies and apoptosis. Western blot analysis was performed to confirm the myricetininduced expression of apoptosisrelated proteins. The levels of cleaved PARP and Bax proteins were increased, and that of Bcl2 was decreased. The levels of proteins in the mitogenactivated protein kinase (MAPK) pathway were examined to confirm the mechanism of myricetininduced apoptosis, and it was found that the expression levels of phosphorylated cJun Nterminal kinase (pJNK) and phosphorylated mitogenactivated protein kinases (pp38) were increased, whereas that of phosphorylated extracellularregulated kinase (pERK) was decreased. It was also demonstrated that myricetin induced autophagy by promoting autophagyrelated proteins such as microtubuleassociated protein 1A/1Blight chain 3 (LC 3) and beclin 1. In addition, 3methyladenine (3MA) was used to evaluate the association between cell viability and autophagy in cells treated with myricetin. The results showed that simultaneous treatment with 3MA and myricetin promoted the apoptosis of breast cancer cells. Furthermore, treatment with a JNK inhibitor reduced cell viability, promoted Bax expression, and reduced the expression of pJNK, Bcl2, and LC 3II/I. These results suggest that myricetin induces apoptosis via the MAPK pathway and regulates JNKmediated autophagy in SKBR3 cells. In conclusion, myricetin shows potential as a natural anticancer agent in SKBR3 cells.
Assuntos
Apoptose , Flavonoides , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Flavonoides/farmacologia , HumanosRESUMO
BACKGROUND: In today's work scenario, the number of shift workers, including those in night shifts, is increasing. Shift work can adversely affect workers' health in the long run, but studies on the relationship between shift work and depression have shown inconsistent results. This study aimed to determine whether the number of night/shift workers at risk of depression, as predicted by the Patient Health Questionnaire-9 (PHQ-9), is higher than that of day workers. METHODS: This study was conducted based on data from the 6th and 7th Korea National Health and Nutrition Examination Survey, 2014, 2016, and 2018. Work schedules were classified into 2 types: day work and night/shift work. This study used the PHQ-9, a self-reported depression screening test, to identify workers at risk of depression. Statistical analysis was performed using SPSS 26.0, and descriptive statistics, χ2 test, and logistic regression analysis were employed. RESULTS: After adjusting for age, educational level, working hours per week, and income, men engaging in night/shift work were at a higher risk of depression (odds ratio [OR]: 1.407, 95% confidence interval [CI]: 0.937-2.113). The same was confirmed for women (OR: 1.564, 95% CI: 1.176-2.081). CONCLUSIONS: Our results showed that the OR for those engaged in night/shift work with a PHQ-9 score of 10 or more increased. Considering the large volume of psychiatric history and symptoms in Korea, additional research is needed. Additionally, further discussion on ways to provide realistic help to night/shift workers is warranted.
RESUMO
Owing to the ineffectiveness of the currently used therapies against melanoma, there has been a shift in focus toward alternative therapies involving the use of natural compounds. This study assessed the anticancer effects of oleanolic acid (OA) and its ability to induce apoptosis in A375SM and A375P melanoma cells in vivo. Compared to the control group, viability of A375P and A375SM cells decreased following OA treatment. In OA-treated A375SM and A375P cells, 4',6-diamidino-2-phenylindole staining showed an increase in the apoptotic body, and flow cytometry revealed increased number of apoptotic cells compared to that in the control group. OA-treated A375SM cells exhibited an increased expression of the apoptotic proteins, cleaved poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma (Bcl)-2-associated X protein (Bax) as well as decreased expression of the antiapoptotic protein Bcl-2 compared to that in the control group. In OA-treated A375P cells, expression patterns of cleaved PARP and Bcl-2 were similar to those in OA-treated A375SM cells; however, no difference was reported in the expression of Bax compared to that in the control group. Additionally, OA-treated melanoma cells showed decreased expression of phospho-nuclear factor-κB (p-NF-κB), phospho-inhibitor of nuclear factor-κBα (p-IκBα), and phospho-IκB kinase αß than that in the control group. Moreover, immunohistochemistry showed a comparatively decreased level of p-NF-κB in the OA-treated group than that in the control group. Xenograft analysis confirmed the in vivo anticancer effects of OA against A375SM cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed an increased number of TUNEL-positive cells in the OA-treated group compared to that in the control group. In conclusion, the study results suggest that OA induces apoptosis of A375SM and A375P cells in vitro and apoptosis of A375SM cells in vivo. Furthermore, the in vitro and in vivo anticancer effects were mediated by the NF-κB pathway.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Ácido Oleanólico/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Rim/citologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Subunidade p50 de NF-kappa B/metabolismo , Neoplasias/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Silymarin is a purified mixture of four isomeric flavonoids extracted from the seeds and fruit of the milk thistle plant, Silybum marianus (L.). Silymarin exhibits a wide variety of biological effects and is commonly used in traditional medicine. Therefore, the anticancer effects of silymarin on human breast cancer cells were investigated to determine its pharmacological mechanisms in vitro and in vivo. The viability and proliferation of MDA-MB- 231 and MCF-7 breast cancer cells were investigated using MTT and wound healing assays. Silymarin decreased the viability and proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner. The number of apoptotic bodies, as shown by DAPI staining, was increased in a concentration-dependent manner, indicating that silymarin induces apoptosis. Additionally, changes in the expression levels of apoptosis-related proteins were demonstrated in human breast cancer cells using western blotting. Silymarin increased the levels of Bax, cleaved poly-ADP ribose polymerase, cleaved caspase-9 and phosphorylated (p-)JNK, and decreased the levels of Bcl-2, p-P38 and p-ERK1/2. Furthermore, the inhibitory effects of silymarin on MCF-7 tumor growth were investigated. In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF-7 tumor growth was inhibited without organ toxicity. In MCF-7 tumors, silymarin induced apoptosis and decreased p-ERK1/2 levels, as assessed using a TUNEL assay and immunohistochemistry. These results indicated that silymarin inhibited breast cancer cell proliferation both in vitro and in vivo by modulating the MAPK signaling pathway. Therefore, silymarin may potentially be used as a chemo-preventive or therapeutic agent.
RESUMO
Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, exhibits pharmacological effects against inflammation, ulcers, infections, and tumors. In the present study, we aimed to investigate the antitumor effects of shikonin on the human melanoma cell line, A375SM, and in an in vivo mouse xenograft model. We examined the anticancer effects of shikonin by in vitro experiments (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, 4',6-diamidino-2-phenylindole (DAPI) stain, annexin V/ propidium iodide (PI) stain, and protein analysis of apoptosis and mitogen-activated protein kinase (MAPK) pathways). Further, the anticancer effect in vivo was confirmed through a xenograft model. Our results showed that shikonin inhibited the proliferation of melanoma cells in a dose-dependent manner. In addition, shikonin significantly increased nucleus and chromatin condensation and early/late apoptosis. Shikonin also increased the pro-apoptotic proteins and decreased the anti-apoptotic proteins. Additionally, shikonin was overexpressed in MAPK pathways. Investigation of the effects of shikonin in a mouse xenograft model not only showed decreased A375SM tumor volume but also increased apoptosis as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, pathologic changes were not observed in the liver and kidney of mice. Collectively, the study indicated that shikonin inhibited the proliferation of the human melanoma cells by inducing apoptosis, mediated by MAPK pathway and that it is a potential candidate for an anticancer drug against melanoma cancer.