L-rhamnose and L-fucose suppress cancer growth in mice

Tomšík, Pavel; Soukup, Tomáš; Čermáková, Eva; Mičuda, Stanislav; Niang, Mohamed; Suchá, Lenka; Řezáčová, Martina

doi:10.2478/s11535-010-0087-0

Cited by 26 publications

(29 citation statements)

References 35 publications

(41 reference statements)

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“…The differences in glucuronic acid quantities between the cultures were consistent with the decrease in zeta potential values. Interestingly, a significant increase in glucose and galactose residues (5-and 2-fold increases, respectively) and the presence of rhamnose (1.5 mol%), a neutral sugar with immunosuppressor activity (45), were detected in capsular PS isolated from the chronologically old culture.…”

Section: Resultsmentioning

confidence: 99%

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

et al. 2011

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Does the age of a microbial cell affect its virulence factors? To our knowledge, this question has not been addressed previously, but the answer is of great relevance for chronic infections where microbial cells persist and age in hosts. Cryptococcus neoformans is an encapsulated human-pathogenic fungus notorious for causing chronic infections where cells of variable age persist in tissue. The major virulence factor for C. neoformans is a polysaccharide (PS) capsule. To understand how chronological age could impact the cryptococcal capsule properties, we compared the elastic properties, permeabilities, zeta potentials, and glycosidic compositions of capsules from young and old cells and found significant differences in all parameters measured. Changes in capsular properties were paralleled by changes in PS molecular mass and density, as well as modified antigenic density and antiphagocytic properties. Remarkably, chronological aging under stationary-phase growth conditions was associated with the expression of ␣-1,3-glucans in the capsule, indicating a new structural capsular component. Our results establish that cryptococcal capsules are highly dynamic structures that change dramatically with chronological aging under prolonged stationary-phase growth conditions. Changes associated with cellular aging in chronic infections could contribute to the remarkable capacity of this fungus to persist in tissues by generating phenotypically and antigenically different capsules.

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Section: Resultsmentioning

confidence: 99%

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

et al. 2011

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“…35 The potential value for therapy is enhanced by lack of toxicity observed in our mice and in previously reported animal and human studies. 36 Additionally, low-molecular-weight fucoidan (LMWF), a group of fucose-enriched sulphated polysaccharides extracted from seaweed, was shown to have a protective effect on I/R injury in mice, 37 though the mechanism was not fully explained. 25 Previous cancer studies have shown that IP injections of l-fucose are not detrimental in mice up to a level of 5 g/kg (approximately 160 mg).…”

Section: Discussionmentioning

confidence: 99%

l ‐Fucose prevention of renal ischaemia/reperfusion injury in Mice

et al. 2019

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In a recent study, we identified a fucosylated damage‐associated ligand exposed by ischemia on renal tubule epithelial cells, which after recognition by collectin‐11 (CL‐11 or collectin kidney 1 (CL‐K1)), initiates complement activation and acute kidney injury. We exploited the ability to increase the local tissue concentration of free l‐fucose following systemic administration, in order to block ligand binding by local CL‐11 and prevent complement activation. We achieved a thirty‐five‐fold increase in the intrarenal concentration of l‐fucose following an IP bolus given before the ischemia induction procedure ‐ a concentration found to significantly block in vitro binding of CL‐11 on hypoxia‐stressed renal tubule cells. At this l‐fucose dose, complement activation and acute post‐ischemic kidney injury are prevented, with additional protection achieved by a second bolus after the induction procedure. CL‐11−/− mice gained no additional protection from l‐fucose administration, indicating that the mechanism of l‐fucose therapy was largely CL‐11‐dependent. The hypothesis is that a high dose of l‐fucose delivered to the kidney obstructs the carbohydrate recognition site on CL‐11 thereby reducing complement‐mediated damage following ischemic insult. Further work will examine the utility in preventing post‐ischemic injury during renal transplantation, where acute kidney injury is known to correlate with poor graft survival.

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“…Interestingly, oral administration of L-fucose was found to successfully increase fucosylation in the patient with leukocyte adhesion deficiency type II (LAD II), a rare inherited disorder of fucose metabolism [51][52][53]. Moreover, tumour growth, mitotic activity and metastatic setting were greatly suppressed by daily intraperitoneal injection of L-fucose in the Ehrlich carcinoma mice [53]. Our results further suggest that the sensitivity to TRAIL can be simulated after elevated expression of FUT3 or FUT6 in tumour cells, which is mainly mediated via DR5 as evidenced by the enhanced sensitivity to DHER of these cells.…”

Section: Discussionmentioning

confidence: 99%

Death receptor 5 is activated by fucosylation in colon cancer cells

et al. 2019

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The remarkable pro‐apoptotic properties of tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) have led to considerable interest in this protein as a potential anticancer therapeutic. However, TRAIL is largely ineffective in inducing apoptosis in certain cancer cells, and the mechanisms underlying this selectivity are unknown. In colon adenocarcinomas, posttranslational modifications including O‐ and N‐ glycosylation of death receptors were found to correlate with TRAIL‐induced apoptosis. Additionally, mRNA levels of fucosyltransferase 3 (FUT3) and 6 (FUT6) were found to be high in the TRAIL‐sensitive colon adenocarcinoma cell line COLO 205. In this study, we use agonistic receptor‐specific TRAIL variants to dissect the contribution of FUT3 and FUT6‐mediated fucosylation to TRAIL‐induced apoptosis via its two death receptors, DR4 and DR5. Triggering of apoptosis by TRAIL revealed that the low FUT3/6‐expressing cells DLD‐1 and HCT 116 are insensitive to DR5 but not to DR4‐mediated apoptosis. By contrast, efficient apoptosis is mediated via both receptors in high FUT3/6‐expressing COLO 205 cells. The reconstitution of FUT3/6 expression in DR5‐resistant cells completely restored TRAIL sensitivity via this receptor, while only marginally enhancing apoptosis via DR4 at lower TRAIL concentrations. Interestingly, we observed that induction of the salvage pathway by external administration of l‐fucose restores DR5‐mediated apoptosis in both DLD‐1 and HCT 116 cells. Finally, we show that fucosylation influences the ligand‐independent receptor association that leads to increased death inducing signalling complex (DISC) formation and caspase‐8 activation. Taken together, these results provide evidence for the differential impact of fucosylation on signalling via DR4 or DR5. These findings provide novel opportunities to enhance TRAIL sensitivity in colon adenocarcinoma cells that are highly resistant to DR5‐mediated apoptosis.

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L-rhamnose and L-fucose suppress cancer growth in mice

Cited by 26 publications

References 35 publications

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

l ‐Fucose prevention of renal ischaemia/reperfusion injury in Mice

Death receptor 5 is activated by fucosylation in colon cancer cells

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