CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Shao-Jun Zheng,Xiao-Han Diao,Xiao-Yan Gao,Nai-Dong Chen
Dendrobium officinale polysaccharides (DOP) exhibit anticancer potential against colorectal cancer (CRC), yet their mechanisms remain unclear. This study investigated DOP's effects on HCT-116 cells. DOP dose- and time-dependently inhibited proliferation and induced apoptosis, evidenced by elevated cleaved caspase-3/-9, poly ADP-ribose polymerase (PARP), Bax, and reduced Bcl-2. Concurrently, DOP activated autophagy (increased LC3-II/I, Beclin-1; decreased p62) via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) suppression. Combining DOP with the autophagy inhibitor chloroquine enhanced apoptosis (higher cleaved PARP, Bax; lower Bcl-2) and reactivated PI3K/Akt/mTOR signaling. These findings demonstrate DOP inhibits CRC by dual induction of apoptosis and autophagy blockade through PI3K/Akt/mTOR inhibition, with autophagy suppression synergistically augmenting apoptosis. The study highlights DOP's translational potential as a functional food or adjuvant therapy, proposing a novel combinatorial strategy for CRC treatment. Graphical Dendrobium officinale polysaccharides (DOP) inhibit HCT-116 colorectal cancer cell proliferation and induce apoptosis by upregulating cleaved caspase-3/-9, PARP, and Bax while downregulating Bcl-2. DOP activates autophagy via PI3K/Akt/mTOR inhibition. Combining DOP with chloroquine enhances apoptosis, revealing autophagy blockade as a synergistic anticancer mechanism.
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PubMed
高影响因子
STARCH-STARKE
·
2017
·
IF 1.837
Dan-Ting Yin,Xin-Huai Zhao
The aim of this study was to assess the potential impact of 10 exogenous strains on acid production of maize resistant starch (RS) and xylo-oligosaccharides (XOS) during in vitro fermentation and on anti-colon cancer activities of fermentation products. Maize RS and XOS were fermented in vitro by the fecal extract from healthy adults in the absence and presence of one exogenous strain culture. Fermentation products were measured for their acetate, propionate, butyrate, and lactate contents, and growth inhibition on human colon carcinoma (HCT-116) cells. These strains in general conferred fermentation products with increased acetate, propionate, and butyrate contents, enhanced lactate conversion, and different growth inhibition on HCT-116 cells. Correlation analysis results demonstrated that butyrate and lactate contents of fermentation products made respective positive and negative contribution to the measured growth inhibition ( p < 0.05); however, acetate and propionate contents made an insignificant contribution to the measured growth inhibition ( p > 0.05). These results were mostly consistent with those from confirmation trials using standard acid solutions for the cells. It is highlighted that these strains had beneficial intervention in colonic fermentation of maize RS and XOS and anti-cancer activities of fermentation products, rendering lower lactate and higher butyrate contents and especially higher anti-colon cancer activities.
研究领域:
营养学
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微生物学
·
癌症研究
·
食品科学
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高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
·
2018
·
IF 2.317
Dan-Ting Yin,Yu Fu,Xin-Huai Zhao
Inulin was fermented by adult faecal microbiota and 10 exogenous strains for 24 or 48 h. The contents of acetate, propionate, butyrate and lactate were quantified in the fermented products, and the growth-inhibitory and apoptosis-inducing effects on a human colon cell line (HCT-116 cells) were assessed. Most of these strains increased contents of acetate, propionate and butyrate, and promoted lactate conversion. Correlation analysis suggested that butyrate and lactate in the fermentation products were positively and negatively correlated with the measured inhibition ratios (p < .05). The results were mostly consistent with the verification trial results using standard acid solutions. The fermentation products could cause apoptosis via inducing DNA fragmentation and increasing total apoptotic populations in the treated cells. Moreover, the fermentation products with higher growth-inhibitory activities demonstrated the increased apoptosis-inducing properties. In conclusion, these strains could cooperate with adult faecal microbiota to confer inulin fermentation products with higher anti-colon cancer activity.
研究领域:
微生物学
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癌症研究
·
胃肠病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shu-Fang Li,Teng-Gen Hu,Hong Wu
A colon-targeted delivery system that can efficiently deliver and release quercetin is essential to improve its bioavailability. We previously found that hydrophobic ethyl cellulose (EC) nanofibers could efficiently deliver quercetin to colon, but the release of quercetin was limited. To address this problem, hydrophilic gelatin (GN) was used as a regulator, and quercetin-loaded nanofibers with different mass ratios of EC to GN (3:1, 1:1, 1:2, 1:3) were fabricated by electrospinning. All nanofibers had a cylindrical morphology and high encapsulation efficiency (over 94 %), and there existed molecular interactions among quercetin, EC, and GN. The high GN content reduced the thermal stability of nanofibers but increased their surface wettability. Besides, these nanofibers had good stability in acidic and aqueous foods. Importantly, the release of quercetin in the simulated gastrointestinal fluid was <3 %. The addition of GN was beneficial to the release of quercetin in colon, and nanofibers with EC to GN being 1:3 had a more preferable release performance. The anticancer activity of nanofibers against HCT-116 cells was proved by inhibiting cell viability through the induction of apoptosis. Therefore, these nanofibers are potential carriers for efficient colon-targeted delivery of bioactive compounds in the food industry.
研究领域:
药学
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生物医学工程
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材料科学
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癌症研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shu-Fang Li,Teng-Gen Hu,Yuan-Bao Jin,Hong Wu
In this study, the feasibility of shellac nanofibers as carrier system for colonic delivery of quercetin was evaluated. Firstly, the nanofibers without and with different amounts (2.5 %, 5.0 %, and 7.5 %) of quercetin were fabricated using pure shellac as a carrier by electrospinning. The morphology of nanofibers was bead-shape confirmed by SEM. FTIR, XRD, and DSC analysis showed that quercetin was encapsulated into shellac nanofibers, forming an amorphous complex. The molecular docking simulation indicated quercetin bound well to shellac through hydrogen bonding and van der Waals forces. These nanofibers had higher thermal stability than pure quercetin, and their surface wettability exhibited a pH-responsive behavior. The loading capacity of quercetin varied from 2.25 % to 6.84 % with the increased amount of quercetin, and it affected the stability of nanofibers in food simulants by measuring the release profiles of quercetin. The shellac nanofibers had high gastrointestinal stability, with a minimum quercetin release of 16.87 % in simulated digestive fluids, while the remaining quercetin was delivered to the colon and was released gradually. Moreover, the nanofibers exerted enhanced anticancer activity against HCT-116 cells by arresting cell cycle in G0/G1 phase and inducing cell apoptosis. Overall, shellac nanofibers are promising materials for colon-targeted delivery of active compounds.
研究领域:
药学
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纳米技术
·
药物递送系统
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癌症研究
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材料科学
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DOI
PubMed
高影响因子
Current Research in Food Science
·
2022
·
IF 6.269
Ya-Hui Yu,Li Wang,Qiang Zhang,Xiao-Nan Zhang,Xin-Huai Zhao
The soluble and non-digestible longan ( Dimocarpus longan Lour . ) polysaccharides (LP) with Se content less than 0.01 g/kg were extracted and selenylated chemically with the HNO 3 –Na 2 SeO 3 system, to prepare two selenylated products namely SeLP1 and SeLP2 with enhanced Se contents of 1.46 and 4.79 g/kg, respectively. LP, SeLP1, and SeLP2 were then measured and compared for their saccharide features and bioactivity in human colon carcinoma HCT-116 cells. Compared with LP, both SeLP1 and SeLP2 contained more neutral saccharides, but showed reduced uronic acid content and undetectable sulfate. Moreover, SeLP1 and especially SeLP2 in the cells showed higher activities than LP, reflected by their enhanced capacity to inhibit cell growth, alter cell morphology, and suppress cell colony formation. Compared with LP, SeLP1 and especially SeLP2 were also more capable of promoting intracellular reactive oxygen species and Ca 2+ levels, causing mitochondrial membrane potential loss, or inducing cell apoptosis via up- and down-regulating the eight apoptosis-related genes and proteins. Overall, the performed chemical selenylation of LP resulted in obvious changes in these saccharide features and simultaneously enhanced the anti-cancer activity of the selenylated products against the cells clearly, while a higher selenylation extent of the selenylated products consistently caused higher activity towards the cells. The results of this study thus highlighted that this chemical selenylation is applicable when aiming to enhance the bioactivities of natural polysaccharides.
研究领域:
药理学
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癌症研究
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生物化学
·
细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Zhen Zhang,Hongbo Wang,Zhijun Zhang,Yaoyao Zhang,Huajing Sun,Xi Chen,Jiayu Gu,Yanling Gong
Small interfering RNA (siRNA)-based therapy, which silences disease-associated genes, has emerged as a potential therapeutic strategy for various disorders, including cancer. Lipid nanoparticles (LNPs) have become a leading platform for efficient siRNA delivery. SOX9, a family member of SRY-related high-mobility-group box (SOX) transcription factors, plays an important role in the pathogenesis and progression of colorectal cancer (CRC). Here, we developed cRGDfK peptide-modificed LNPs (R-LNPs) composed of DLin-MC3-DMA, DMG-PEG, DSPC, DSPE-PEG-cRGDfK, and cholesterol for the targeted delivery of SOX9 siRNA (siSOX9) in CRC treatment. The formulation, delivery, and antitumor effect on CRC in vitro and in vivo were explored. The optimized R-LNPs exhibited favorable physicochemical properties including a uniform particle size (159.6 ± 0.93 nm), low polydispersity index (PDI = 0.207 ± 0.016), near-neutral zeta potential (2.74 ± 0.35 mV), and high encapsulated efficiency (90.71 ± 1.63%). Additionally, R-LNPs demonstrated sustained and controlled in vitro release and good serum stability. The prepared R-LNPs were efficiently uptaken by HCT-116 via clathrin, lipid rafts, and caveolae dependent endocytosis and macropinocytosis. Subsequently, R-LNPs were colocalized with lysosomes before escaping into the cytoplasm, ensuring effective siRNA release. In vivo distribution studies confirmed tumor-specific accumulation for R-LNPs in HCT-116 xenograft models. Functionally, R-LNPs loading siSOX9 inhibited the proliferation, migration, and invasion of HCT-116 cells and Caco-2 cells (P < 0.05 or 0.01) and inhibited tumor growth and proliferation in tumor-bearing mice (P < 0.05 or 0.01). The antitumor effects were attributed to the silence of SOX9, which subsequently downregulated key oncogenic mediators, including β-catenin, cyclin D1, and c-Myc (P < 0.05 or 0.01). Furthermore, R-LNPs demonstrated favorable safety in in vivo application. In conclusion, our cRGDfK-modified LNPs loading siSOX9 represent a promising targeted therapeutic strategy for CRC, offering both efficacy and biocompatibility.
研究领域:
药剂学
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肿瘤学
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纳米技术
·
分子生物学
·
药物递送
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生物技术
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DOI
PubMed
高影响因子
Cancer Medicine
·
2021
·Vol. 10
·期 10
·3358-3372
·
IF 4.452
Dingsheng Liu,Chunsheng Chen,Mingming Cui,Hong Zhang
Recent studies have identified microRNAs (miRNAs) as a compelling novel class of biomarker in colorectal cancer (CRC) development and metastasis. Here, we demonstrated that the level of plasma exosomal miR-140-3p in CRC patients was lower than that in healthy controls. The decreased miR-140-3p level was also observed in CRC patients with liver metastasis. The expression of miR-140-3p in CRC tissues were significantly lower than that in matched normal tissues. Functionally, miR-140-3p overexpression suppressed proliferation, migration, invasion, and β-catenin nuclear translocation, as well as promoted apoptosis in LoVo cells, while inhibition of miR-140-3p reversed these cellular processes in HCT 116 cells. Notably, BCL9 and BCL2 were recognized as direct targets of miR-140-3p. BCL9 knockdown abrogated miR-140-3p inhibitor-induced effects on HCT 116 cells with decreased proliferation, migration, and invasion. BCL2 knockdown increased apoptosis of miR-140-3p inhibitor-transfected HCT 116 cells. In vivo experiments revealed that miR-140-3p overexpression inhibited tumor growth in LoVo xenograft model and diminished metastatic nodules in nude mice liver. Taken together, this work supports that miR-140-3p exerts as a tumor suppressor in CRC progression via targeting BCL9 and BCL2, and suggests miR-140-3p-BCL9/BCL2 axis may be applied in miRNA-based therapy and prognostication of CRC.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
·
遗传学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Shuangni Zhao,Le Van Minh,Na Li,Vasil M. Garamus,Ulrich A. Handge,Jianwen Liu,Rongguang Zhang,Regine Willumeit-Römer,Aihua Zou
The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200 nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2021
·Vol. 32
·期 45
·455101
·
IF 3.874
Xiaojing Yang,Di-Feng Chen,Lin-Song Li,Xue-Jie Zhao,Mei-Xia Zhao
In this study, a nanodrug carrier (mesoporous silica nanoparticle (MSN)-SS-cysteamine hydrochloride (CS)-hyaluronic acid (HA)) for targeted drug delivery was prepared using MSNs, in which HA was used as a targeting ligand and blocking agent to control drug release. Coumarin is a fluorescent molecule that targets mitochondria. Two conjugates (XDS-DJ and 5-FUA-4C-XDS) were synthesized by chemically coupling nitrogen mustard and 5-fluorouracil with coumarin, which was further loaded into MSN-SS-CS-HA nanocarriers. MTT analysis demonstrated that the nanocomposite MSN-SS-CS@5-FUA-4C-XDS/HA displayed stronger cytotoxicity toward HCT-116 cells than HeLa or QSG-7701 cells. Furthermore, MSN-SS-CS@5-FUA-4C-XDS/HA was able to target the mitochondria of HCT-116 cells, causing decreased mitochondrial membrane potential and excessive production of reactive oxygen species. These results indicate that MSN-SS-CS@5-FUA-4C-XDS/HA has the potential to be a nanodrug delivery system for the treatment of colon cancer.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2019
·
IF 6.054
Ran Zhang,Xue-Qing Song,Rui-Ping Liu,Zhong-Ying Ma,Jing-Yuan Xu
As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of “dual-prodrug” by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10–17, named Fuplatin, exhibited much higher cytotoxicity against the tested cancer cells while lower cytotoxicity toward the human normal lung cells than free drugs or their combinations. Among them, 14 enhanced cellular accumulation with 62- and 825-fold amount of oxaliplatin and 8 at 9 h, respectively, significantly induced DNA damage and cell apoptosis, and inhibited migration and invasion in HCT-116 cells. Compound 14 arrested the cell cycle at S and G2 phases and up-regulated thymidylate synthase and p53, consistent with the results of the combination, suggesting 14 adopted a collaborative mode of 5-FU and oxaliplatin to kill cancer cells. In vivo, compound 14 showed high antitumor effect and no observable toxicity in NOD/SCID mice bearing HCT-116 tumors.
研究领域:
肿瘤学
·
药理学
·
化疗
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shu-Fang Li,Teng-Gen Hu,Hong Wu
Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6–98.5 %) and loading capacity (1.4–4.1 %) varied with increasing the initial quercetin addition amount (2.5–7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
药物递送系统
·
癌症研究
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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）