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
·
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
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
·
癌症研究
·
生物化学
✓ 已验证
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
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2022
·Vol. 14
·期 4
·741-750
·
IF 5.265
Gao Xiaoxi,Zhang Yuhong,Mu Guangqing,Xu Yunpeng,Wang Xinmiao,Tuo Yanfeng,Qian Fang
The aim of the present study was to investigate the in vitro antioxidant potential of Bacillus coagulans T242. B. coagulans T242 showed better antioxidant activities, including the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging ability, lipid peroxidation inhibiting ability and reducing ability, than those exerted by Lactobacillus rhamnosus GG (LGG). B. coagulans T242 positively regulated the expression of the nuclear factor erythroid 2-relatedfactor 2/Kelch-like ECH-associated protein-1 (Nrf2/Keap1) pathway-related proteins (Nrf2, Keap1, heine oxygenase-1 (HO-1)); increased antioxidant enzymes (glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD)); reduced the content of malondialdehyde (MDA) level; decreased the expression of inflammatory-related cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α); and thus increased the survival rate in 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-damaged HT-29 cells. This study proved that B. coagulans T242 exerted antioxidative effects by quenching oxygen free radicals and activating the Nrf2 signaling pathway in HT-29 cells.
研究领域:
微生物学
·
细胞生物学
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药理学
·
分子生物学
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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
·
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
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Shi-Kang Zhou,Yi Zhang,Yong-Hui Ju,Qiao Zhang,Da Luo,Yu-Dan Cao,Wei-Feng Yao,Yu-Ping Tang,Li Zhang
The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1) , 5- O -benzoyl-20-deoxyingenol (2) , 20-deoxyingenol (3) , 3- O -(2’ E ,4’ E -decadienoyl)-20- O -acetylingenol (4) , 20- O -(2’ E ,4’ Z -decadienoyl)ingenol (5) , and ingenol (6) , in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min −1 . Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1 , 2 , 4 , and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC 50 > 200 μM). Meanwhile, 1 , 2 , 4 , 5 , and 6 significantly increased the expression of AQP3 protein ( p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.
研究领域:
药理学
·
毒理学
·
分析化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Long Ma,Xiuqi Cao,Haiyue Wang,Kui Lu,Ying Wang,Chunhao Tu,Yujie Dai,Yuanyuan Meng,Yuyin Li,Peng Yu,Shuli Man,Aipo Diao
Human flap endonuclease 1 (hFEN1) is instrumental in DNA replication and repair. It is able to cleave the 5′ single-stranded protrusion (also known as 5′ flap) resulting from strand displacement reactions. In light of its crucial functions, hFEN1 is now deemed as a nontrivial target in the DNA damage response system for anticancer drug development. Herein, we report that myricetin and some natural flavonoids are able to inhibit hFEN1. Structure–activity relationship, inhibitory mechanisms, molecular docking, and cancer cell-based assays have been performed. Our original findings expand the activity of flavonoids and may pave the way for flavonoid-assisted targeted cancer therapy.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Yuxing Guo,Tao Zhang,Jinjin Gao,Xiaoxiao Jiang,Mingxuan Tao,Xiaoqun Zeng,Zhen Wu,Daodong Pan
This research sought to assess the anticancer effects of Lactobacillus acidophilus CICC 6074 and its underlying mechanism of action. L. acidophilus CICC 6074 inhibited HT-29 cell activity and induced its apoptosis in a dose- and time-dependent manner. HT-29 cells exposed to L. acidophilus CICC 6074 showed mitochondrial membrane potential (ΔΨm) loss, as well as Cyt c is released from the mitochondria into the cytoplasm, causing Bax, Caspase-9 and Caspase-3 to be up-regulated and Bcl-2 to be down-regulated. To further explore the mechanism by which L. acidophilus CICC 6074 achieves its anti-cancer effect, a HT-29 cell-induced colon cancer mouse model was used. Compared with a colon cancer model control group, the high-dose L. acidophilus CICC 6074 group showed obvious colon cancer cell apoptosis as measured by histological morphology, electron microscopy, and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. An in vivo study showed that L. acidophilus CICC 6074 induced colon cancer apoptosis by up-regulating Bax, down-regulating Bcl-2, releasing Cyt c from the mitochondria into the cytoplasm, and activating Caspase-3 and Caspase-9. These results demonstrate that L. acidophilus CICC 6074 exerts anticancer effects via the activation of mitochondrial pathways which then induce apoptosis. The research could provide new ideas and theoretical basis for development of probiotics functional food market.
研究领域:
肿瘤学
·
微生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Phytochemistry Letters
·
2023
·
IF 1.7
Min-Li Zhang,Yi-Min Li,Zi-Xuan Zhao,Xiang-Yuan Li,Zhao-Cui Sun,Guo-Xu Ma,Mei-Hua Yang,Xu-Dong Xu,Xiao-Feng Zhang,Hai-Feng Wu,Qiong-Yu Zou,Nelbon Giloi
Phytochemical investigation of the whole plant of Actaea vaginata led to the isolation of five cycloartane triterpene glycosides , including three new Actaeoside A−C ( 1 − 3 ) along with two known analogues, beesiosides E ( 4 ) and N ( 5 ). Their structures were elucidated by NMR , HRESIMS and chemical analysis. The cytotoxicity of compounds ( 1 − 5 ) was assayed against HT-29 and HepG2 cancer cell lines. All the isolates showed moderate degrees of inhibitory activity against the HT-29 with IC 50 values in a range of 18.2–27.8 μM.
研究领域:
植物化学
·
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
NATURAL PRODUCT RESEARCH
·
2018
·
IF 1.928
Jingjing Liang,Xiaogang Peng,Jia Zhou,Ming Zhou,Hanli Ruan
One new diarylheptanoid (3S)-3′, 4″-epoxy-1-(4′-hydroxylphenyl)-7-(3″-hydroxylphenyl) heptane-3-hydroxy (1), together with eleven known ones (2–12), was isolated from the fresh pericarps of Juglans sigillata. Their structures were elucidated on the basis of extensive spectroscopic methods, including HR-ESI-MS, 1D and 2D-NMR. All isolates were evaluated for their cytotoxic activities in vitro against the growth of human cancer cells lines HT-29 and MCF-7 by MTT assay.
研究领域:
植物化学
·
药理学
·
肿瘤学
✓ 已验证
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
·
药学
·
生物技术
✓ 已验证
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
·
分子生物学
✓ 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）