The anti-melanoma activity of inulin in mice

Cooper, Penny; Carter, Margrit

doi:10.1016/0161-5890(86)90076-3

Cited by 41 publications

(21 citation statements)

References 7 publications

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“…The first therapeutic isoform (gamma inulin (GI)) was followed by the more active delta inulin (DI), which is the clinically preferred option . The biological significance of these newer, relatively insoluble inulin forms, in contrast to the more soluble alpha and beta isoforms, is their clinical utility as potent, safe and well-tolerated immune modulators, most notably as vaccine adjuvants (Cooper and Steele 1988;Frazer et al 1999;Silva et al 2004;Lobigs et al 2010;Cooper and Petrovsky 2011;Cristillo et al 2011;Layton et al 2011;Gordon et al 2012;Honda-Okubo et al 2012;Larena et al 2013;Saade et al 2013) but also with anti-cancer effects (Cooper and Carter 1986b;Cooper 1993;Korbelik and Cooper 2007). DI is also a useful reagent for exploring and regulating cellular immune functions in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

2013

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In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1 H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

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Section: Introductionmentioning

confidence: 99%

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

2013

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“…Owing to these properties, there is also interest in g-inulin as vaccine adjuvant, its safety for human use has been verified (Frazer et al, 1999). It has also been known for some time that intralesional g-inulin treatment elicits antitumour responses and it was demonstrated that this results from the complement-activating effect (Cooper and Carter, 1986b). Positive responses following multiple treatment regimens were reported with mouse tumours (B16 melanoma model), squamous cell carcinoma in sheep, equine sarcoids, and spontaneous malignancies in dogs (Cooper and Carter 1986b;Cooper, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been known for some time that intralesional g-inulin treatment elicits antitumour responses and it was demonstrated that this results from the complement-activating effect (Cooper and Carter, 1986b). Positive responses following multiple treatment regimens were reported with mouse tumours (B16 melanoma model), squamous cell carcinoma in sheep, equine sarcoids, and spontaneous malignancies in dogs (Cooper and Carter 1986b;Cooper, 1993). Our recent related work has shown that complement component C3 and other complement proteins accumulate in tumours treated by PDT (Cecic and Korbelik, 2002;Cecic et al, 2005), and that complement system recognises PDT-treated tumour cells as their target .…”

Section: Discussionmentioning

confidence: 99%

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

Korbelik

Cooper

2006

Br J Cancer

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Host response elicited by photodynamic therapy (PDT) of cancerous lesions is a critical contributor to the clinical outcome, and complement system has emerged as its important element. Amplification of complement action was shown to improve tumour PDT response. In search of a clinically relevant complement activator for use as a PDT adjuvant, this study focused on g-inulin and examined its effects on PDT response of mouse tumours. Intralesional g-inulin (0.1 mg mouse À1 ) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of g-inulin was further enhanced by IFN-g pretreatment. Tumour C3 protein levels, already elevated after individual PDT or g-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant g-inulin proved highly effective in reducing recurrence rates following PDT using four different photosensitisers (BPD, ce6, Photofrin, and mTHPC). At 3 days after PDT plus g-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforingranzyme pathway. This study demonstrates that g-inulin is highly effective PDT adjuvant and suggests that by amplifying the activation of complement system, this agent potentiates the development of CTL-mediated immunity against PDT-treated tumours.

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“…These and similar alterations of the colonic microflora have been reported to have an inhibitory action on tumor incidence and/or growth (Reddy et al, 1973;Reddy and Rivenson, 1993). Moreover, it has been reported that a cell-wall preparation from Bifidobacterium infantis has a tumor-suppressive effect (Tsuyuki et al, 1991;Sekine et al, 1994), and at least one paper has shown an anti-melanoma activity of inulin (Cooper and Carter, 1986). Rumney and Rowland (1995) reviewed the potential anti-carcinogenic effect of non-digestible oligosaccharides, and concluded that 2 lines of evidence are suggestive of such an effect: (i) ''certain biomarkers thought to be affected by cancer risk are beneficially affected by oligosaccharide consumption in animals and man''; (ii) ''they increase the numbers of lactic-acid bacteria in the gut, bacteria which show antigenotoxic and anti-carcinogenic effects''.…”

Section: Discussionmentioning

confidence: 99%

Growth inhibition of transplantable mouse tumors by non-digestible carbohydrates

1997

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The protective role of dietary components in carcinogenesis and cancer development is a topic of major interest (Williams and Dickerson, 1990;Roberfroid, 1991;Milner, 1994). The identification of such components, the understanding of their mechanism of action as well as their development and use in human diet is one of the objectives of functional food science, which is a part of modern nutrition.A functional food is a food which contains one or a combination of components that interact with physiological functions in the body so as to improve them, and that justify functional or health claims (Roberfroid, 1995(Roberfroid, , 1997. The development of such functional foods starts with identification of an interaction between a food component or a food ingredient and a particular function in the body, followed by proper understanding of the mechanism of such positive interaction, and leading to the demonstration of a beneficial effect in humans which, in due course, may justify claims (Roberfroid, 1995).Among the many cited physiological functions of non-digestible carbohydrates, one of the most important is probably the capacity to prevent carcinogenesis in its early stages. Immunomodulation by carbohydrates or their bacterial metabolites, or by the intestinal bacteria that they selectively promote, is reported as a possible mechanism of cancer prevention (Nossal, 1993;Perdigon et al., 1993).Much work has been done to identify components (e.g., carotenoids, allylic sulfides) or ingredients (e.g., dietary fibers) in diet with the capacity to prevent initiation and possibly promotion of carcinogenesis. These products are classified as anti-carcinogens (Wattenberg, 1992).But many fewer experiments have been performed to identify dietary components that could help the organism slowing down or stopping the growth and development of an already existing population of neoplastic cells. It has however been reported that live bacteria which are used as probiotics (Fuller, 1992), as well as fractions of their membrane preparations, may inhibit the growth of various types of tumors in experimental models involving i.p., s.c. or i.m. implantation of tumor cells (Reddy et al., 1973(Reddy et al., , 1983Kato et al., 1981;Ayebo et al., 1981;Koo and Rao, 1991;Tsuyuki et al., 1991) or chemically induced carcinogenesis (Reddy and Rivenson, 1993).Fructans such as chicory inulin and oligofructose belong to a new class of functional food ingredients (Roberfroid, 1995). Being non-digestible in the upper part of the gastrointestinal tract, they flow into the colon where they selectively promote Bifidobacteria . Because they selectively promote the growth of certain types of bacteria, they are classified as ''pre-biotics'' (Gibson and Roberfroid, 1995). Moreover, recent work in our group with rats has demonstrated that supplementing diet with chicory fructans modulates hepatic lipogenesis possibly via or concomitantly with changes in insulin sensitivity (Fiordaliso et al., 1995;Kok et al., 1996). Like the other non-digestible carbohydrates...

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The anti-melanoma activity of inulin in mice

Cited by 41 publications

References 7 publications

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

Growth inhibition of transplantable mouse tumors by non-digestible carbohydrates

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