Antitumor and Adjuvant Activity of λ-carrageenan by Stimulating Immune Response in Cancer Immunotherapy

Luo, Min; Shao, Bin; Nie, Wen; Wei, Xiawei; Li, Yuli; Wang, Bilan; He, Zhiyao; Liang, Xiao; Ye, Tinghong; Wei, Yuquan

doi:10.1038/srep11062

Cited by 94 publications

(81 citation statements)

References 51 publications

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“…Various polysaccharides, including fucoidan, ascophyllan and λ-carrageenan, have shown immune activation and anti-cancer effects [3, 19, 23, 24]. In this study, we showed that pullulan, a polysaccharide purified from Aureobasidium pullulans , promoted the activation of BMDCs in vitro and of spleen DCs in vivo, and induced anti-cancer immune responses.…”

Section: Discussionmentioning

confidence: 66%

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Zhang

Kwak

et al. 2016

Oncotarget

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Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines.

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Section: Discussionmentioning

confidence: 66%

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Zhang

Kwak

et al. 2016

Oncotarget

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“…In addition, carrageenan extracted from red seaweed of the Rhodophyceae family and L. papillosa showed cytotoxicity via inhibition of cell proliferation and induction of apoptosis in human intestinal cancer, breast cancer, and liver cancer cells (31,32). Consistent with the anticancer activity, the administration of λ-carrageenan stimulated the immune system via up-regulation of proinflammatory IL17A and TNF-α, thereby stimulating the activities of tumor infiltrating M1 macrophages, dendritic cells, and T lymphocytes (33). Furthermore, a recent study has confirmed that the extracted sulfated carrageenan (ESC) consists of ι-carrageenan, which infers a direct damage to DNA by modulating nuclear condensation and DNA fragmentation in breast cancer MDA-MB-231 cells.…”

Section: Inhibition Of Cancer Cell Proliferation and Survival Bymentioning

confidence: 76%

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

Yun

Kim

2019

Anticancer Res

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Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy. Cancer is one of the leading causes of death and an economic burden worldwide (1). Cancer involves an abnormal proliferation of cells and tissues, and is affected by various risk factors such as age, diet, genetics, and environmental factors (2, 3). It is also caused by the mutation of several cancer-related genes called tumor suppressors and oncogenes (4). Cancer also presents the ability of metastasis and recurrence, which are difficult to treat (5). Although conventional anticancer therapy includes both chemotherapy to induce apoptosis of target cancer cells and surgical therapy to remove tumors, these methods are limited by issues of therapeutic efficacy, safety, and side effects. Thus, it is necessary to develop novel strategies for cancer therapy, and natural products (NPs) are a promising source for novel drug development because they show diverse biological activities and anticancer effects via inhibition of tumor growth by interacting with several signaling pathways (6, 7). NPs have been a useful source of bioactive compounds and play an important role in the discovery and development of drugs. Most NPs, originated from terrestrial microbes, fungi, and plants, have been discovered to possess many pharmacologically active factors and used to treat several human diseases. Some of these are utilized as clinically valuable drugs for anticancer therapy (8-10). However, marine organisms have recently attracted substantial attention because 70% of the earth is covered by water, representing 95% of biodiversity (11-13). NPs derived from marine organisms have been researched for novel bioactive secondary metabolites due to their diverse pharmacological activities. Marine environments are estimated to harbor more than one million species and one billion different types of marine microbes (14). Today, around 28,000 new compounds isolated from marine species, such as algae, seaweed, sponges, and starfish, have been reported, and this species diversity provides a diverse array of secondary metabolic products (15, 16). In this review, we present NPs derived from marine environments, and summari...

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“…Accumulating evidence indicates that κ-CGNs, especially their low-MW degradation products, induce inflammation in the colon, resulting in a range of diseases in cell and animal models, including thrombosis [28][29][30][31], peritonitis [26,[32][33][34], paw edema [35,36], pleurisy [37,38], gastroenterocolitis [39,40], arthritis [41,42], and inflammatory bowel disease. However, CGNs also show positive health effects, such as antitumor [43], antimicrobial [44], and antiviral [45,46]. Removal of sulfate esters from sulfated polysaccharides is considered one of the essential steps for microorganisms in the degradation of sulfurized polysaccharides [47].…”

Section: Discussionmentioning

confidence: 99%

Carrageenan oligosaccharides and their degrading bacteria induce intestinal inflammation in germ-free mouse

Yin

et al. 2020

Preprint

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Background: Carrageenans (CGNs) are widely used in food and pharmaceutical industries. However, the safety of CGNs is still under debate, because degraded CGNs have been reported to promote an intestinal inflammatory response in animal models. Here, we studied the relationship among CGNs, human gut microbiota, and the host inflammatory response.Methods: TLC was selected for detecting the degradation of KCPs by human gut microbiota in vitro batch fermentation system. PCR-DGGE and real time PCR were used for studying bacterial community. ESI-MS was used for KCPs structure analysis. Hematoxylin-eosin staining (HE), immunohistochemistry (IHC) and RNA-seq were used to evaluated the KCPs on host inflammation response in germ-free mice.Results: Thin-layer chromatography (TLC) data showed that CGNs with a molecular weight (Mw) higher than 100 kDa are not degraded by human fecal microbiota, but low Mw CGNs with an Mw around ~4.5 kDa (KCOs) could be degraded by seven of eight human fecal microbiota samples. KCO degrading B. xylanisolvens was isolated from fecal samples, and PCR-DGGE profiling with band sequencing suggested that B. xylanisolvens was the key KCO degrader in the human gut. Two putative κ-carrageenase genes were identified in the genome sequence of B. xylanisolvens. However, their function on KCO degrading was not verified in vitro. And the sulfate group from KCO is not removed after in vitro degradation by human fecal microbiota, as shown by ESI-MS analysis. The effects of KCO and KCO degrading bacteria on the inflammatory response were investigated in germ-free mice. Increased numbers of P-P38-, CD3a-, and CD79a-positive cells were found in the colon and rectum in mice fed with KCO plus KCO degrading bacteria than in mice fed with only KCO or only B. xylanisolvens and E. coli, as shown by RNA-Seq analysis, HE staining, and IHC. Conclusion: Our data suggested that the presence of KCO degrading bacteria promote the pro-inflammatory effects of CGNs.

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Antitumor and Adjuvant Activity of λ-carrageenan by Stimulating Immune Response in Cancer Immunotherapy

Cited by 94 publications

References 51 publications

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

Carrageenan oligosaccharides and their degrading bacteria induce intestinal inflammation in germ-free mouse

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