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1.
J Med Food ; 27(4): 330-338, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387002

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 Células
2.
Biomed Pharmacother ; 172: 116216, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295755

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-2
3.
Toxicol Res ; 40(1): 45-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223666

RESUMO

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.

4.
Anticancer Res ; 43(7): 3047-3056, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37351981

RESUMO

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 Tumoral
5.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555388

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 farmacológico
6.
J Am Chem Soc ; 144(34): 15519-15528, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35972994

RESUMO

Although interest in stabilized α-helical peptides as next-generation therapeutics for modulating biomolecular interfaces is increasing, peptides have limited functionality and stability due to their small size. In comparison, α-helical ligands based on proteins can make steric clash with targets due to their large size. Here, we report the design of a monomeric pseudo-isolated α-helix (mPIH) system in which proteins behave as if they are peptides. The designed proteins contain α-helix ligands that do not require any covalent chemical modification, do not have frayed ends, and importantly can make sterically favorable interactions similar to isolated peptides. An optimal mPIH showed a more than 100-fold increase in target selectivity, which might be related to the advantages in conformational selection due to the absence of frayed ends. The α-helical ligand in the mPIH displayed high thermal stability well above human body temperature and showed reversible and rapid folding/unfolding transitions. Thus, mPIH can become a promising protein-based platform for developing stabilized α-helix pharmaceuticals.


Assuntos
Peptídeos , Proteínas , Sequência de Aminoácidos , Dicroísmo Circular , Humanos , Peptídeos/química , Conformação Proteica em alfa-Hélice , Dobramento de Proteína , Estrutura Secundária de Proteína
7.
Biomedicines ; 10(7)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35884773

RESUMO

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.

8.
Food Sci Anim Resour ; 42(4): 609-624, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35855272

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.

9.
Heliyon ; 8(5): e09309, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35521506

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.

10.
Int J Mol Med ; 49(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35234274

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 , Humanos
11.
Chem Biol Interact ; 347: 109619, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34364837

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 Xenoenxerto
12.
Oncol Lett ; 21(6): 492, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33968208

RESUMO

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.

13.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33403388

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.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Melanoma/patologia , Naftoquinonas/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Marcação In Situ das Extremidades Cortadas , Melanoma/enzimologia , Melanoma/metabolismo , Camundongos , Proteínas de Neoplasias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Mol Med Rep ; 22(6): 4877-4889, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174048

RESUMO

Apigenin, an aromatic compound, exhibits antioxidant, anti­inflammatory and anti­viral effects. The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM. Therefore, melanoma cells were treated with apigenin to determine its anti­proliferative and survival effects, using wound healing and MTT assays. The results revealed that melanoma cell viability was decreased in a dose­dependent manner. Furthermore, chromatin condensation, indicating apoptosis, was significantly increased in a dose­dependent manner, as demonstrated by DAPI staining. In addition, increased apoptosis rate following treatment with apigenin was confirmed by Annexin V­propidium iodide staining. The changes in the expression levels of apoptosis­related proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis. The results demonstrated that the protein expression levels of Bcl­2 were decreased, whereas those of Bax, cleaved poly ADP­ribose polymerase, cleaved caspase­9 and p53 were upregulated in a dose­dependent manner in apigenin­treated cells compared with those noted in untreated cells. In addition, in apigenin­treated A375P cells, phosphorylated (p)­p38 was upregulated and p­extracellular signal­regulated kinase (ERK), p­c­Jun N­terminal kinase (JNK) and p­protein kinase B (Akt) were downregulated. However, in A375SM cells, apigenin treatment increased p­ERK and p­JNK and decreased p­p38 and p­Akt protein expression levels. Subsequently, the inhibitory effect of apigenin on tumor growth was investigated in vivo. Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenin­treated groups compared with the control group. Additionally, a TUNEL assay was performed to detect apoptotic cells. Immunohistochemical staining also revealed elevated p­ERK expression in the apigenin­treated group compared with the control group. Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen­activated protein kinase signaling pathways.


Assuntos
Apigenina/farmacologia , Melanoma/metabolismo , Animais , Apigenina/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , China , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Melanoma/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
15.
Nutr Res Pract ; 13(6): 543-554, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31814930

RESUMO

BACKGROUND/OBJECTIVES: The elderly are reported to have a high prevalence of nutritional anemia when they have lower intakes of nutrients or chronic diseases. This study was conducted to compare nutritional status according to nutritional anemia and to determine associations between nutritional anemia and chronic diseases in Korean elderly. MATERIALS/METHODS: This study utilized data on 3,258 elderly aged ≥ 65 years gathered during the 6th Korea National Health and Nutrition Examination Survey 2013-2015. Subjects were divided into nutritional anemia (NA) group (n = 415) and non-NA group (n = 2,843) by hemoglobin concentration. Nutrient intakes were assessed using dietary intake data obtained using the 24-hour recall method. The odds ratios (ORs) for nutritional anemia by chronic diseases were determined. Statistical analysis was performed using SPSS Ver. 23.0. RESULTS: Of 3,258 subjects, 12.7% had nutritional anemia. Intakes of potatoes, pulses, and mushrooms by males and potatoes, fruits, meats, eggs, and seafood by females were significantly lower in NA group than in non-NA group. The proportion of the subjects whose intakes of protein, vitamin A, vitamin B1, vitamin B2, niacin, and iron less than estimated average requirement (EAR) were significantly higher in NA group compared to non-NA group. After adjusting for age, the number of family members, energy intake, and alcohol drinking, ORs for nutritional anemia in the subjects with diabetes and myocardial infarction or angina pectoris were significantly higher by 1.74 times and 1.59 times as compared to the subjects without those diseases, respectively. However, ORs for nutritional anemia in the subjects with obesity, abdominal obesity, and hypertriglyceridemia were significantly lower by 0.64 times, 0.60 times, and 0.59 times as compared to the subjects without those diseases, respectively. CONCLUSIONS: The results of this study suggested that nutritional management should be done to enable the Korean elderly to consume foods with high hematopoietic nutrients density to prevent nutritional anemia. Korean elderly need to make regular efforts to check for nutritional anemia.

16.
Oncol Rep ; 42(5): 1904-1914, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485597

RESUMO

Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti­inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration­dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose­dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin­induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)­JNK and p­p38, and cleaved poly­ADP ribose polymerase, and decreased the levels of Bcl­2 and p­ERK1/2 in a concentration­dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor­inhibitory effect. Immunohistochemical staining revealed elevated expression of p­JNK and p­p38 as well as reduced expression of p­ERK1/2 associated with silymarin­treatment. Silymarin was revealed to reduce tumor growth through inhibition of p­ERK and activation of p­p38 and p­JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Silimarina/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Silimarina/farmacologia , Neoplasias Gástricas/metabolismo , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Adv Exp Med Biol ; 1155: 205-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468399

RESUMO

The purpose of this study was to investigate consumption patterns and perform Importance-Performance Analysis (IPA) of selective attributes of Home Meal Replacement (HMR) products according to taurine-related nutritional knowledge levels in Koreans aged 40-64 years as a basis for developing additional HMR products. The study included 793 adults (297 males and 496 females) who had experience in consuming HMR products and who lived in Seoul and its metropolitan areas, Korea. Data were collected using self-administered questionnaires. Statistical analysis was performed by using the SPSS 18.0 program. The subjects were classified into a high-level group (HG, 467 adults) and low-level group (LG, 326 adults) based on their taurine-related nutritional knowledge scores. Analysis of HMR consumption patterns showed that the frequency of HMR consumption in the HG was one to two times a month in 41.1% of the subjects and once every 3-4 months in 22.7% of the subjects, whereas, in the LG, it was one to two times a month in 39.3% of the subjects and four to six times a month in 24.5% of the subjects. With regarding to the reasons for purchasing HMR products, there was no significant difference between HG and LG (p = 0.089). The IPA analysis of HMR selective attributes included factor analysis of 14 selective attributes that were divided into three factors: 'convenience and taste', 'reliability and health', and 'brand and awareness'. The average importance scores of the first (p < 0.01), second (p < 0.001), and third (p < 0.01) factors in the HG were significantly higher than those in the LG. In addition, the average satisfaction with the first factor (p < 0.01) in the HG was significantly higher than that in the LG. Based on the IPA results, the selective attributes with low satisfaction and high importance were price, origin, food additives, and nutrient content in both the HG and LG. In the second IPA quadrant was safety, but only in the LG. Multiple regression analysis revealed that the importance of the reliability and health factor and the satisfaction with the convenience and taste factor were positively influenced by the subject's taurine-related nutritional knowledge score. These results suggest that reliability and safety of HMR products need to be improved to meet the expectations of Korean consumers aged 40 years and older with a high level of taurine-related nutritional knowledge. Therefore, there is a need to produce HMR products that use safe and reliable food ingredients.


Assuntos
Alimentos Fortificados , Conhecimentos, Atitudes e Prática em Saúde , Taurina/administração & dosagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , República da Coreia , Inquéritos e Questionários , Paladar
18.
Adv Exp Med Biol ; 1155: 215-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468400

RESUMO

It has been reported that taurine intake in the past may have a positive effect on present cognitive function in the elderly. The purpose of this cross-sectional study was to investigate the need to develop an elderly-friendly home meal replacement (EF-HMR) containing taurine for the prevention of dementia in Korean adults aged 40-84 years. Study subjects included 481 adults 40-49 years group, 319 adults 50-64 years group, and 181 elderly group (65-84 years old) residing in Seoul and its metropolitan area, Korea. Data were collected from adults aged 40-64 years by self-administered questionnaires and from elderly through face-to-face interviews. Statistical analysis was performed using SPSS 18.0. The level of need for EF-HMR was significantly higher in 40-49 years and 50-64 years groups compared to the elderly group (p < 0.001). With regard to the preferred EF-HMR taste, the needs for less salty (p < 0.01) and less sweet (p < 0.001) foods were significantly higher in 40-49 years group compared to the elderly group. The main factors of consideration in the development of EF-HMR were nutrition, taste, and freshness. The level of need for EF-HMR containing taurine was significantly lower in those 40-49 years and 50-64 years groups compared to the elderly group (p < 0.01). If an EF-HMR containing taurine for prevention of dementia was developed, willingness to buy such a food was significantly higher in the elderly group than in those 40-49 years and 50-64 years groups (p < 0.01). Regarding cooked EF-HMR containing taurine, semi-prepared and ready-made meals were preferred in 71.1% and 25.4% in 40-49 years group, 69.6% and 22.6% in 50-64 years group, and 47.0% and 33.7% in the elderly group, respectively (p < 0.001). EF-HMR containing taurine sales unit sizes containing 3 servings or 1 serving was preferred by 37.2% and 26.3% of all subjects. The preferred places to purchase EF-HMR (in descending order of super-supermarket (mart), supermarket, and convenience store) were the same among the age groups. Therefore, it is necessary to understand the diversity present in the needs and purchasing characteristics of adults involved purchasing EF-HMR containing taurine, and there is a need to develop age-specific customized products for the elderly and for Korean adults 40-64 years old.


Assuntos
Demência/prevenção & controle , Alimentos Fortificados , Taurina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Estado Nutricional , República da Coreia
19.
Adv Exp Med Biol ; 1155: 223-230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468401

RESUMO

This study aimed to estimate the dietary taurine intake and its food sources in Korean's aged between 19 and 29 years. The study included 619 participants (292 males and 327 females) who had provided data via a 24-h recall method to the 2015 Korea National Health and Nutrition Examination Survey (KNHANES). Dietary taurine intake and the sources of dietary taurine were estimated by using CAN-Pro 4.0 software. Statistical analysis was performed by using SPSS 20.0. Average height and weight of the subjects was 174 cm and 73.5 kg in males and 161 cm and 56.4 kg in females, respectively. The prevalence of obesity in males was significantly higher compared to females (p < 0.001). Overall, the nutrient intakes of subjects were higher than the dietary reference intakes for Korean's (KDRIs). In particular, phosphorus and sodium intakes of males and females were higher, whereas, potassium and calcium intakes of males and females were lower than the KDRIs. The average intake of taurine 327.3 mg by males was significantly higher compared to 245.1 mg by females (p < 0.05). With regard to dietary taurine intake from the main food groups, meat (p < 0.001), vegetable (p < 0.001), beverages and alcohol (p < 0.05), and cereal (p < 0.001), in males was significantly higher compared to females. This study showed that 19-29 years old Korean young adults had a high intake of taurine due to high intake of protein. However, since high intake of meat can lead to chronic disease, it is necessary to provide nutrition education to increase the intake of fishes and shellfishes as a taurine source food.


Assuntos
Dieta , Inquéritos Nutricionais , Taurina/administração & dosagem , Adulto , Feminino , Alimentos , Humanos , Masculino , República da Coreia , Adulto Jovem
20.
Adv Exp Med Biol ; 1155: 231-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468402

RESUMO

The purpose of this research is to investigate the effects of dietary taurine supplementation on blood and urine taurine concentrations of the elderly women with dementia. Subjects were 31 female elderly with dementia hospitalized in a geriatric hospital. They were divided randomly into control group and dietary taurine supplemented group. Basically, same meals were served to both groups. Scorched rice water without taurine were served to control group. Scorched rice water containing 3 g of taurine were reserved to taurine group with lunch similarly. Food ingredients containing high concentration of taurine were eliminated from the meal menu. Blood and urine samples were obtained from each subject at the beginning of study, after 2 week and 4 weeks in the morning fasting state. Taurine concentrations in serum and urine were measured as taurine-fluorescamine derivatives using high performance liquid chromatography (HPLC). Data were analyzed using SPSS 20.0. The average taurine concentrations in serum and urine of subjects were 89.2 ± 9.5 µM and 876.7 ± 97.1 µM at the beginning. After 4 weeks, the taurine concentrations in serum and urine of dietary taurine supplemented group were 218.0 ± 15.6 µM and 6502.6 ± 380.6 µM, which were significantly higher compared to control group. Dietary taurine supplemented group showed positive changes in the score on language and execute performance. So taurine supplementation can provide beneficial effects to the elderly and the elderly with dementia.


Assuntos
Demência/sangue , Demência/urina , Suplementos Nutricionais , Taurina/administração & dosagem , Idoso , Feminino , Humanos , Taurina/sangue , Taurina/urina
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