scholarly journals Selective Suppression of Cell Growth and Programmed Cell Death-Ligand 1 Expression in HT1080 Fibrosarcoma Cells by Low Molecular Weight Fucoidan Extract

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 421 ◽  
Author(s):  
Kiichiro Teruya ◽  
Yoshihiro Kusumoto ◽  
Hiroshi Eto ◽  
Noboru Nakamichi ◽  
Sanetaka Shirahata

Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from Cladosiphon novae-caledoniae Kylin, exhibits various biological activities, including anticancer effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.

1997 ◽  
Vol 82 (9) ◽  
pp. 3148-3155
Author(s):  
Wei Yuan ◽  
Linda C. Giudice

Abstract Although extensive investigation on follicular apoptosis (programmed cell death) has been conducted in the infraprimate ovary, there is little information regarding apoptosis and its relationship to follicular status in the human. In this study, apoptosis was investigated in 116 human ovarian follicles (primordial to dominant) and 5 corpora lutea from a total of 27 premenopausal women. Follicles and corpora lutea were evaluated for the presence of DNA fragmentation, characteristic of apoptosis, by two methods: in situ hybridization using 3′ end-labeling of DNA with digoxigenin-labeled nucleotides and subsequent digoxigenin antibody and peroxidase staining, and/or biochemical analysis of low molecular weight DNA laddering. Follicle functional status was evaluated by determining follicle sizes and follicular fluid androgen/estrogen (A/E) ratios. No apoptosis was observed in 67 primordial, primary, or secondary follicles. Positive staining for DNA fragmentation was found in a few granulosa cells in 0.1- to 2-mm follicles, whereas abundant staining in granulosa was detected in 2.1- to 9.9-mm follicles. In contrast, no DNA fragmentation was detected in dominant follicles (10–16 mm). The frequency of apoptosis in follicles was calculated to be 37% in 0.1- to 2-mm follicles, 50% in 2.1- to 5-mm follicles, and 27% in 5.1- to 9.9-mm follicles. Abundant low molecular weight DNA laddering was only found in androgen-dominant follicles and not in estrogen-dominant follicles. Positive staining for DNA fragmentation and low molecular weight DNA laddering were observed in degenerating but not healthy-appearing corpora lutea. In the former, DNA fragmentation was found primarily in large luteal cells. These data suggest that follicular atresia in human ovary results from normal programmed cell death and primarily occurs in the granulosa cell layers of the early antral and <10-mm antral follicles primarily. Furthermore, because apoptosis occurs as early as the 200-mm stage, follicle selection may begin as early as the initial formation of the antrum. The results also suggest that degeneration of the corpus luteum occurs by apoptotic mechanisms.


1987 ◽  
Vol 58 (04) ◽  
pp. 1068-1072 ◽  
Author(s):  
P Toulon ◽  
J F Vitoux ◽  
C Leroy ◽  
T Lecomte ◽  
M Roncato ◽  
...  

SummaryWe compared in six patients successively treated with an unfractionated heparin (UFH) and a low molecular weight heparin (LMWH) the variations in plasma anti-Xa activity, measured in a chromogenic assay, during a 36 h constant infusion. The values varied in a wider range during UHF infusion, but remained in the therapeutic range except once in one patient. No circadian rhythm could be demonstrated in our six patients. LMWH infusion yielded very constant anti-Xa circulating activities. In both cases, there were no significant modifications of three proteins with high heparin affinity (antithrombin III, heparin cofactor II, histidine-rich glycoprotein).Our results suggest that the circadian rhythm of the biological activities previously observed in patients treated with constant heparin infusion using clotting method is due to other factors than heparin itself.


Author(s):  
Makoto Ogata

Abstract Carbohydrates play important and diverse roles in the fundamental processes of life. We have established a method for accurately and a large scale synthesis of functional carbohydrates with diverse properties using a unique enzymatic method. Furthermore, various artificial glycan-conjugated molecules have been developed by adding these synthetic carbohydrates to macromolecules and to middle and low molecular weight molecules with different properties. These glycan-conjugated molecules have biological activities comparable to or higher than those of natural compounds, and present unique functions. In this review, several synthetic glycan-conjugated molecules are taken as examples to show design, synthesis and function.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 369
Author(s):  
Joanna Wawszczyk ◽  
Katarzyna Jesse ◽  
Sławomir Smolik ◽  
Małgorzata Kapral

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.


2008 ◽  
Vol 6 (9) ◽  
pp. 6
Author(s):  
A. Strasser ◽  
A. Villunger ◽  
P. Bouillet ◽  
E.M. Michalak ◽  
L.A. O'Reilly ◽  
...  

1993 ◽  
Vol 128 (1) ◽  
pp. 88-94 ◽  
Author(s):  
Nobuyoshi Kokawa ◽  
Mareo Yamoto ◽  
Kenichi Furukawa ◽  
Ryosuke Nakano

We performed partial purification of low molecular weight luteinizing hormone binding inhibitor from porcine follicular fluids and examined its biological activities. Following ultrafiltration, gel filtration and anion exchange of the pooled porcine follicular fluids, low molecular weight fractions (500–10,000 MW) inhibited [125I]hLH binding to porcine granulosa cells in a dose-dependent manner. The binding inhibition kinetics study revealed that the luteinizing hormone binding inhibitor may indicate a non-competitive inhibition with [125I]hLH binding. In vitro bioassay using adult mouse testicular interstitial cells revealed that the partially purified luteinizing hormone binding inhibitor reduced ovine LH-stimulated testosterone and cAMP production in a dose-dependent manner, whereas the luteinizing hormone binding inhibitor did not affect basal production of testosterone and cAMP. The inhibitory activity was heat stable and did not disappear with activated charcoal adsorption. The results of the present study suggest that the luteinizing hormone binding inhibitor may play an important role as an ovarian non-steroidal regulator modulating the receptor binding of LH and LH-mediated steroidogenesis.


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