Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal–epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

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Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22158041 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8041

Author(s):

Ching-Wen Huang ◽

Yen-Cheng Chen ◽

Tzu-Chieh Yin ◽

Po-Jung Chen ◽

Tsung-Kun Chang ◽

...

Keyword(s):

Cell Cycle ◽

Molecular Weight ◽

Cell Viability ◽

Signaling Pathway ◽

Complementary Therapy ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Tumor Cell Migration ◽

Anti Cancer

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-–5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal–epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.

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Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648988 ◽

1994 ◽

Vol 72 (06) ◽

pp. 942-946 ◽

Cited By ~ 20

Author(s):

Raffaele Landolfi ◽

Erica De Candia ◽

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Armando Antinori ◽

...

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Primary Source ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Heparin Administration ◽

To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue I. Effects of Heparin Fractions

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653429 ◽

1981 ◽

Vol 46 (03) ◽

pp. 612-616 ◽

Cited By ~ 18

Author(s):

U Schmitz-Huebner ◽

L Balleisen ◽

F Asbeck ◽

J van de Loo

Keyword(s):

Molecular Weight ◽

Day Treatment ◽

Gel Filtration ◽

Weight Fraction ◽

In Vivo Studies ◽

Low Molecular Weight ◽

High Molecular Weight Fraction ◽

Platelet Factor ◽

Heparin Fractions

SummaryHigh and low molecular weight heparin fractions obtained by gel filtration chromatography of sodium mucosal heparin were injected subcutaneously into six healthy volunteers and compared with the unfractionated substance in a cross-over trial. Equal doses of 5,000 U were administered twice daily over a period of three days and heparin activity was repeatedly controlled before and 2, 4, 8 hrs after injection by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of subcutaneously administered fractionated heparin on platelet function was examined on three of the volunteers. The results show that s.c. injections of the low molecular weight fraction induced markedly higher anti-Xa activity than injections of the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the high molecular weight fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA production, while the low molecular weight fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of platelet Factor 4 in plasma. During the three-day treatment periods, no side-effects and no significant changes in the response to heparin injections were detected.

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In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa

Molecules ◽

10.3390/molecules21050625 ◽

2016 ◽

Vol 21 (5) ◽

pp. 625 ◽

Cited By ~ 28

Author(s):

Xiaoxiao Liu ◽

Yong Liu ◽

Jiejie Hao ◽

Xiaoliang Zhao ◽

Yinzhi Lang ◽

...

Keyword(s):

Molecular Weight ◽

Chondroitin Sulfate ◽

Sea Cucumber ◽

Low Molecular Weight ◽

Anti Cancer ◽

Cucumaria Frondosa

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Low Molecular Weight Hydroxyethyl Chitosan-Prednisolone Conjugate for Renal Targeting Therapy: Synthesis, Characterization and In Vivo Studies

Theranostics ◽

10.7150/thno.3705 ◽

2012 ◽

Vol 2 (11) ◽

pp. 1054-1063 ◽

Cited By ~ 20

Author(s):

Xia-kai He ◽

Zhi-xiang Yuan ◽

Xiao-juan Wu ◽

Chao-qun Xu ◽

Wan-yu Li

Keyword(s):

Molecular Weight ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Targeting Therapy

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In Vivo Studies On The Inhibition Of Coagulation By Fractionated Heparin

10.1055/s-0038-1652306 ◽

1981 ◽

Author(s):

U Schmitz-Huebner ◽

L Balleisen ◽

F Asbeck ◽

J van de Loo

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Gel Filtration ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Chromogenic Substrate ◽

Serotonin Content ◽

Heparin Activity ◽

Heparin Fractions

Recent investigations suggest that low molecular weight heparin may have advantages over conventional heparin with regard to the prevention of venous thrombosis and haemorrhagic side effects.High (HMW) and low (LMW) molecular weight heparin fractions with mean MWs of 16,000 and 8,800 respectively, obtained by gel filtration chromatography of sodium mucosal heparin (B. Braun Melsungen), were injected subcutaneously into six volunteers and compared with the unfractionated substance in a cross-over trial. Doses of 5,000 U were administered twice daily over a period of three days and heparin activity was controlled before injection and 2,4,8 hours afterwards by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of fractionated heparin on platelet function was examined. The results show that the LMW fraction induced markedly higher anti-Xa activity than the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the HMW fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA-production, while the LMW fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of PF IV, whereas the serotonin content of platelets determined at the same time increased.It is concluded that s.c. injections of LMW heparin induce relatively high levels of anti-Xa activity without leading to sensitive platelet activation or to major effects on overall clotting tests.

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Reactions of certain trichloromethyl sulfenyl fungicides with low-molecular-weight thiols. In vivo studies with cells of Saccharomyces pastorianus

Journal of Agricultural and Food Chemistry ◽

10.1021/jf60171a034 ◽

1970 ◽

Vol 18 (5) ◽

pp. 823-826 ◽

Cited By ~ 16

Author(s):

Malcolm R. Siegel

Keyword(s):

Molecular Weight ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Saccharomyces Pastorianus

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Nanoformulation of a Novel Pyrano[2,3-c] Pyrazole Heterocyclic Compound AMDPC Exhibits Anti-Cancer Activity via Blocking the Cell Cycle through a P53-Independent Pathway

Molecules ◽

10.3390/molecules24030624 ◽

2019 ◽

Vol 24 (3) ◽

pp. 624 ◽

Cited By ~ 2

Author(s):

Xuanrong Sun ◽

Longchao Zhang ◽

Mengshi Gao ◽

Xiangjie Que ◽

Chenfeng Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cancer Cells ◽

Biological Activities ◽

Polymeric Micelle ◽

In Vivo Studies ◽

One Pot ◽

Anti Cancer ◽

G2 Phase ◽

Anti Tumor Activity

Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of P21 gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed.

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