Nutrients
·
2022
·Vol. 14
·期 9
·1710
·
IF 6.706
Ya-Hui Yu,Zhi-Mei Tang,Cen Xiong,Fei-Fei Wu,Jun-Ren Zhao,Xin-Huai Zhao
The selenylated polysaccharides chemically belong to the organic Se-conjugated macromolecules and have recently been attracting more and more attention due to their potential to promote body health or prevent cancers. Longan (Dimocarpus longanL.), as a subtropical fruit, contains soluble and non-digestible polysaccharides that are regarded with health care functions in the body. In this study, the longan polysaccharides (LP) were obtained via enzyme-assisted water extraction, and then chemically selenylated using a reaction system composed of HNO3–Na2SeO3to yield two selenylated products, namely, SeLP1 and SeLP2, with Se contents of 1.46 and 4.79 g/kg, respectively. The anti-cancer effects of the three polysaccharide samples (LP, SeLP1, and SeLP2) were thus investigated using the human colon cancer HT-29 cells as the cell model. The results showed that SeLP1 and SeLP2 were more able than LP to inhibit cell growth, alter cell morphology, cause mitochondrial membrane potential loss, increase intracellular reactive oxygen and [Ca2+]ilevels, and induce apoptosis via regulating the eight apoptosis-related genes and proteins including Bax, caspases-3/-8/-9, CHOP, cytochrome c, DR5, and Bcl-2. It was thereby proven that the selenylated polysaccharides could induce cell apoptosis via activating the death receptor, mitochondrial-dependent, and ER stress pathways. Collectively, both SeLP1 and SeLP2 showed higher activities than LP in HT-29 cells, while SeLP2 was consistently more active than SeLP1 in exerting these assessed anti-cancer effects on the cells. In conclusion, this chemical selenylation covalently introduced Se into the polysaccharide molecules and caused an enhancement in their anti-cancer functions in the cells, while higher selenylation extent was beneficial to the activity enhancement of the selenylated products.Keywords:longan polysaccharides;selenylation;HT-29 cells;anti-cancer activity;apoptosis
研究领域:
药理学
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癌症研究
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生物化学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2021
·Vol. 22
·期 4
·1-9
·
IF 2.967
Xing-Hua Zhou,Jian Kang,Zhen-Dong Zhong,Yue Cheng
Endoplasmic reticulum stress (ERS) and autophagy are important pathways, which induce apoptosis of tumor cells. Osthole has been demonstrated to exert anticancer effects via the induction of apoptosis in several human colon cancer lines, but the mechanism underlying its involvement in the induction of ERS and autophagy in the human HT‑29 colorectal cancer cell line remains unknown. The present study aimed to identify the possible signaling pathways involved in osthole‑induced apoptosis of HT29 cells. Methodologically, colony formation and Cell Counting Kit‑8 assays were used to assess cell proliferation and viability, respectively, while flow cytometry was performed to investigate apoptosis. Signaling pathways, including apoptosis, autophagy and ERS, were also investigated in the HT‑29 cell line using western blot analysis. The results demonstrated that osthole inhibited cellular proliferation and viability in a dose‑dependent manner. In addition, osthole induced the expression level of proteins associated with mitochondria‑mediated cell apoptosis, autophagy and ERS. The association between autophagy and ERS in osthole‑induced apoptosis in the HT‑29 cell line was further clarified. Inhibiting cell autophagy with the inhibitor, 3‑methyladenine, suppressed osthole‑induced cell apoptosis and enhanced osthole‑induced ERS. By contrast, alleviating ERS with the inhibitor, 4‑phenylbutyric acid attenuated osthole‑induced cell apoptosis and autophagy. In conclusion, osthole could significantly suppress the proliferation and viability of the HT‑29 colorectal cancer cell line and induce cell apoptosis via autophagy and ERS. Furthermore, ERS may play a more important role in osthole‑induced cell apoptosis.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2024
·
IF 2.6
Rongrong Fu,Rui Chang,Andong Peng,Changshun Feng,Weifan Zhu,Yi Chen,Xue Tian,Rui Wang,Hui Yan,Dianlong Jia,Jun Li
To solve the problem of resistance of tumor cells to TRAIL and the inevitable side effects of imatinib during treatment, we successfully prepared a kind of multifunctional liposome that encapsulated imatinib in its internal water phase and inserted TRAIL on its membrane in this study, which named ITLPs. The liposomes appeared uniform spherical and the particle size was approximately 150 nm. ITLPs showed high accumulation in TRAIL-resistance cells and HT-29 tumor-bearing mice model. In vitro cytotoxicity assay results showed that the killing activity of HT-29 cells treated with ITLPs increased by 50% and confirmed that this killing activity was mediated by the apoptosis pathway. Through mechanism studies, it was found that ITLPs arrested up to 32.3% of cells in phase M to exert anti-tumor effects. In vivo anti-tumor study showed that ITLPs achieved 61.8% tumor suppression and little toxicity in the HT-29 tumor-bearing mice model. Overall results demonstrated that codelivery of imatinib and TRAIL via liposomes may be a prospective method in the treatment of the TRAIL-resistance tumor.
研究领域:
肿瘤学
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药学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2018
·
IF 2.583
Shumei Wang,Xue Han,Lanwei Zhang,Yingchun Zhang,Hongbo Li,Yuehua Jiao
The Lactobacillus paracasei subsp. paracasei M5 strain exerted potential anticancer activity through the cell wall. In this study, whole peptidoglycan (WPG) was extracted from the Lactobacillus paracasei subsp. paracasei M5 strain and was evaluated for anticancer effects as well as its properties. SDS-PAGE analysis confirmed the presence of WPG with dominant bands of approximately 14.4 kDa. Further analysis revealed that the amino acids present in the WPG consisted of alanine, glycine, glutamic acid, and lysine in a molar ratio of approximately 8 : 5 : 3 : 3.5. In addition, the cell viability of HT-29 cells with WPG addition was investigated with methyl thiazolyl tetrazolium (MTT) and trypan blue exclusion (TBE) assays, and cell apoptosis was analyzed with a transmission electron microscope, flow cytometry, and semiquantitative RT-PCR. These results showed that WPG exerted cytotoxic effects on colon cancer HT-29 cells in a dose-dependent manner and upregulated proapoptotic genes, while downregulating antiapoptotic genes. The gene expression study definitively revealed that WPG induced a mitochondria-mediated apoptotic pathway.
研究领域:
微生物学
·
癌症生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Suwei Jiang,Hailiang Hu
To explore how chitosan-modified rice porous starch-loaded catechin (CT@RPS/CS) protects HT-29 cells exposed to lead ions. Method: The HT-29 cells were treated differently based on their grouping. The effect of CT@RPS/CS on lead-induced toxicity was evaluated using cell proliferation, apoptosis, oxidative stress index, and cytokine tests. Results: CT@RPS/CS did not affect the activity, cell apoptosis, oxidative stress level, and related cytokines of HT-29 cells. After exposure to lead, CT@RPS/CS has the potential to enhance cellular activity, minimize apoptosis, and decrease the level of oxidative stress. Discussion: CT@RPS/CS not only has no toxicity to cells but also adsorbs lead ions, which protects cells.
研究领域:
食品科学
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毒理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hongyan Lin,Shuaijun Cui,Xinye Xu,Qingqing Chen,Jiazi Ge,Dongxuan Ai,Jie Zhu,Yuheng Tao,Liqun Wang,Lingyu Ruan,Wenhao Ge
18β-Glycyrrhetinic acid (18β-GA) is the main active component of licorice and one of the most promising lead compounds in traditional Chinese herbal medicine. Previous studies have shown that 18β-GA can act as a PPARγ agonist to exert antitumor activity. However, the number of reported 18β-GA derivatives as PPARγ agonists is limited and they have significant toxic side effects, which greatly restricts their application and development. To obtain highly effective and low-toxic PPARγ agonists, through structure-activity relationship (SAR) analysis, we constructed a molecular library of 18β-GA derivatives containing 13,440 compounds and screened out 14 novel 18β-GA ester derivatives. The selected compounds were evaluated for their antitumor activity in vitro. The results showed that most of the compounds exhibited strong anti-proliferative activity against five human cancer cell lines, especially the human colon cancer cell line HT-29, without significant toxicity to normal cell lines. Among them, C1 had the strongest anti-proliferative activity against HT-29, with an IC 50 value of 12.25 μM, which was 12 times higher than that of its parent nucleus 18β-GA. C1 can block the cell cycle of HT-29 cells in G2/M phase, significantly inhibit their migration and induce their apoptosis. Molecular docking and dynamics simulation results suggested that C1 could stably bind to the active pocket of PPARγ. Further PPARγ activity analysis and drug-likeness prediction results indicated that C1 could act as a PPARγ agonist to exert antitumor effects and had certain drug-likeness, which is worthy of further study.
研究领域:
药理学
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药物化学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Shuang Luo,Xiangliang Deng,Qi Liu,Zengfeng Pan,Zhongxiang Zhao,Lian Zhou,Xia Luo
Emodin is an anthraquinone compound derived from Rheum officinale Baill . Several reports showed that emodin had efficacy on acute pancreatitis , keratitis , myocarditis , and rheumatoid arthritis . However, the potency of emodin on ulcerative colitis(UC) remains unclear. In this study, we investigated the effect of emodin on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Our results showed that emodin significantly alleviated the symptoms of DSS-induced UC in mice, involving prevented the loss of body weight and colon shortening, decreased the disease activity index (DAI), intestinal damages and the count of white blood cells (WBC) in peripheral blood. In addition, emodin treatment decreased the level of anti-flagellin antibody in serum and significantly down-regulated the expression of TLR5 and NF-κB p65 in colon of the UC mice. Further study in vitro showed that emodin down-regulated the expression of TLR5 and MyD88 , up-regulated the expression of IκB, inhibited the nuclear translocation of NF-κB p65 and decreased the release of IL-8 in flagellin-stimulated HT-29 cells. These results, for the first time, demonstrated that emodin had the therapeutic potential to ameliorate UC symptoms possibly via regulating the flagellin-TLR5 signaling pathway . Emodin may be a potential candidate ingredient for ulcerative colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yu Zhang,Yan Liu,Yinxing Zhou,Ziming Zheng,Wenqi Tang,Mengzi Song,Jinglin Wang,Kaiping Wang
Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro . SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Li Peng,Hua Xiong,Jiaqi Wang,Rong Tsao,Xin Peng,Li Jiang,Yong Sun
Polyphenol-rich Laird lentil hulls are a byproduct of lentil processing. In the present study, free and bound polyphenols in lentil hulls were analyzed with UHPLC-LTQ-OrbiTrap-MS2, and the anti-inflammatory mechanism of their digestive products was explored based on the NF-κB and Keap1-Nrf2 signaling pathways in the HT-29 cell model. In summary, a total of 27 polyphenols and 5 nonphenolic constituents were identified in free and bound fractions, and among them, catechin glucoside, kaempferol tetraglucoside, procyanidin dimer, and dihydroxybenzoic acid-O-dipentoside were the main polyphenols in the digestive products. These digestive products could reduce inflammatory mediators and exert anti-inflammatory activity by inhibiting NF-κB and activating Keap1-Nrf2 signaling pathways, and there was crosstalk between them, which was a mutual inhibition effect. The results show that polyphenols in lentil hulls are a good source of anti-inflammatory ingredients and have a promising development potential.
研究领域:
食品科学
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药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2023
·
IF 2.8
Zepeng Chen,Qinglong Gu,Ruichao Chen
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.
研究领域:
炎症性肠病
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分子生物学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 8
·1596
·
IF 3.06
Yi Ma,Yunhui Feng,Wanling Zeng,Huibo Luo
This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625–1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0–60 μg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1.Keywords:antioxidant;oxidative stress;anthocyanin;HT-29
研究领域:
食品科学
·
药理学
·
营养学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Kaiying Jia,Xueying Tao,Zhengqi Liu,Hui Zhan,Weijun He,Zhihong Zhang,Zheling Zeng,Hua Wei
In this study exopolysaccharide (EPS) of Enterococcus faecium WEFA23 from healthy infant's feces was yielded as high as 130 mg/L by fermentation. By purification the EPS was further fractioned into A23-1, A23-2, A23-3 and A23-4 on HiTrap Q HP and Superdex G-200 column. As the major purified fractions, A23-2 and A23-4 were analyzed for the preliminary structures and investigated for the biological properties in vitro. The molecular weight of A23-2 and A23-4 was 2.50 × 10 4 Da and 3.23 × 10 4 Da, respectively. A23-2 was composed of mannose, glucose and galactose with a ratio of 1.38:1.00:1.42, while A23-4 consisted of only mannose. The antioxidant ability of A23-2 was significantly higher than that of A23-4, as proved by scavenging test of DPPH radical, hydroxyl radical and superoxide radical. Both A23-2 and A23-4 exhibited strong inhibition against the adhesion of L . monocytogenes CMCC54007 on HT-29 cells no matter for the styles of competition, displacement and exclusion. Notably, for exclusion they had a maximal inhibition rate of 89.85 ± 0.46% and 90.81 ± 2.29%, respectively, at 200 μg/mL.
研究领域:
微生物学
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食品科学
·
生物技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）