Abstract Carnosic acid (CA), the main antioxidant compound of Rosmarinus officinalis L., has been shown to display anticancer activity. However, the molecular mechanisms underlying the anticancer effects of CA remain poorly understood. This study revealed that treatment with CA significantly reduced the cell viability and induced apoptosis in HCT116 cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, -7 and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression. CA inhibited the constitutive phosphorylation, the DNA binding and the reporter gene activity of signal transducer and activator of transcription-3 (STAT3) in HCT116 cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) and Src kinases. Moreover, CA attenuated the expression of STAT3 target gene products, such as survivin, cylcin D1, D2, and D3. Since ROS is a universal entity mediating apoptosis, we examined whether CA induced apoptosis via ROS formation. Treatment with CA generated ROS and pretreatment with ROS scavenger N-acetyl cysteine (NAC) rescued cells from apoptosis by abrogating the inhibitory effect of CA on the activation of JAK2-STAT3 and Src-STAT3 signaling pathways and rescued cells from CA-induced apoptosis by blocking the induction of p53, and the cleavage of caspase-3 and PARP. In conclusion, CA induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway. Citation Format: In Gyeong Chae, Mi-Hee Yu, Ki-Woong Park, Kyung-Soo Chun. Carnosic acid induces apoptosis through inhibition of STAT3 signaling and production of ROS in human colon cancer HCT116 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2015-5566
본 연구에서는 Bacillus subtilis NUC1균주로 발효한 탈지대두 grits 발효물인 FD와 탈지대두 grits에 녹두를 2.5, 5, 10%로 각각 첨가하여 발효한 FDM을 각각 제조하여 in vitro 상에서의 콜레스테롤 개선능을 검색하였다. FD와 FDM군의 콜레스테롤 흡착능을 살펴본 결과, 모든 군에서 70% 이상의 흡착능을 보였다. 특히 2.5% 녹두를 첨가하여 발효시킨 FDM군(2.5% FDM)은 90%의 가장 높은 흡착능을 보였다. 2.5% FDM군은 42%의 HMG-CoA reductase 저해 활성을 보였고, 또한 HepG2 세포를 이용하여 측정한 세포내의 콜레스테롤 함량과 apolipoprotein AⅠ, CⅢ의 개선효과에서도 가장 우수한 개선효과를 보였다. 따라서 2.5% 녹두를 첨가하여 발효시킨 FDM군은 고콜레스테롤 예방에 도움을 줄 것으로 생각된다.
Methanol extract of Zizania latifolia was partitioned with EtOAc, n-BuOH, and H2O. From the EtOAc layers, a new flavonolignan along with a known flavone and three known flavonolignans, tricin (1), salcolin A (2), salcolin B (3), and salcolin C (4), were isolated through repeated silica gel and ODS column chromatography. The chemical structure of the new flavonolignan was determined to be tricin-4'-O-[erythro-β-guaiacyl-(7″-O-methyl)-glyceryl] ether and was named salcolin D (5) based on physicochemical and spectroscopic data, including FT-NMR and ESI-MS. All compounds were isolated for the first time from this plant. Compounds 2-5, tricin derivatives, all exhibited higher anti-inflammatory and anti-allergy activities than tricin. In particular, salcolin D (5) was shown to have the strongest inhibitory activity against LPS-induced NO production in RAW 264.7 cells as well as β-hexosaminidase release in IgE-sensitized RBL-2H3 cells. These results suggest that the presence of tricin derivatives conveys allergy and inflammation treatment ability to Z. latifolia.
Ganoderma applanatum (GA) and related fungal species have been used for over 2000 years in China to prevent and treat various human diseases. However, there is no critical research evaluating the functionality of GA grown using submerged culture technology. This study aimed to evaluate the effects of submerged culture GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1 cells were treated with differentiation inducers in the presence or absence of GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay showed that the GAM extract (0.01–1 mg/mL) was not toxic to 3T3-L1 preadipocyte. Treatment of cells with GAM extracts and its active components significantly decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Western blot analysis results showed that the protein expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract. In addition, adipogenic-specific genes such as perilipin, fatty acid synthase (FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4 (FABP4) decreased in a dose-dependent manner. Quantitative high-performance liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part, through altered regulation of PPARγ, C/EBPα, and SREBP1. These results suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting differentiation of preadipocytes.
Carnosol, an active constituent of rosemary, has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of carnosol remain poorly understood. In the present study, we found that carnosol significantly reduced the viability of human colon cancer (HCT116) cells in a concentration- and time-dependent manner. Treatment of cells with carnosol induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of poly-(ADP-ribose) polymerase (PARP). Incubation with carnosol elevated the expression of Bax and inhibited the levels of Bcl-2 and Bcl-xl. Carnosol induced expression of p53 and inhibited that of murine-double minute-2 (Mdm2). Moreover, carnosol generated reactive oxygen species (ROS), and pretreatment with N-acetyl cysteine abrogated carnosol-induced cleavage of caspase-3 and PARP. The constitutive phosphorylation, the DNA binding and reporter gene activity of signal transducer and activator of transcription-3 (STAT3) was diminished by treatment with carnosol. To further elucidate the molecular mechanisms of STAT3 inactivation, we found that carnosol attenuated the phosphorylation of Janus-activated kinase-2 (Jak2) and Src kinase. Pharmacological inhibition of Jak2 and Src inhibited STAT3 phosphorylation. Furthermore, carnosol attenuated the expression of STAT3 target gene products, such as survivin, cyclin-D1, -D2, and -D3. Taken together, our study provides the first report that carnosol induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway.
$Cr^{3+}$ 및 Se을 첨가하여 수경 재배한 치커리 3종의 에탄올 추출물을 각각 제조하여 추출물별 항산화 활성을 비교 검토하였다. 그 결과 양액만으로 재배한 치커리보다 양액에 Se이나 $Cr^{3+}$을 첨가한 치커리 추출물에서 총 폴리페놀 함량, 총 플라보노이드 함량 및 FRAP 환원능이 증가하였으며, DPPH 라디칼 소거능 및 ABTS 라디칼 소거능도 증가하였다. 특히 Se을 첨가한 치커리보다 $Cr^{3+}$을 첨가한 치커리에서 더 우수한 항산화 활성을 나타내었다. 또한 $Cr^{3+}$을 첨가한 CLER 및 CLE의 경우 ${\alpha}$-glucosidase 저해활성이 있음을 알 수 있었다. 따라서 치커리 추출물의 수경재배 과정에서 양액에 $Cr^{3+}$, Se의 첨가는 치커리의 항산화 활성 및 ${\alpha}$-glucosidase 저해활성 증진에 영향을 주는 것으로 확인되었다. This study was carried out to investigate the effect on the growth and antioxidant activities of Cichorium intybus L.(CLE), Cichorium intybus L. var. folisum 'treviso' (CLET), Cichorium intybus L. var. folisum 'rosaitaliana' (CLER) in hydroponics added with $Cr^{3+}$ or Selenium (Se) for 4 weeks. Total polyphenol, total flavonoids contents and FRAP values of three species of chicory were grown hydroponically with $Cr^{3+}$ or Se were increased. These extracts were also showed stronger DPPH and ABTS scavenging activity than chicory extracts. In particular, chicories added with $Cr^{3+}$ had higher antioxidant activities than chicories added with Se. CLER and CLE extracts added with $Cr^{3+}$ were also showed ${\alpha}$-glucosidase inhibition activities. These results indicate that chicories were cultivated in culture fluid added with $Cr^{3+}$ or Se could be used as high functional vegetables.
Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer’s disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach.
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