The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation

Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance i...

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Main Authors: Min Tang, Leilei Zhai, Juanjuan Chen, Feng Wang, Haimin Chen, Wei Wu
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/9/2044
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author Min Tang
Leilei Zhai
Juanjuan Chen
Feng Wang
Haimin Chen
Wei Wu
author_facet Min Tang
Leilei Zhai
Juanjuan Chen
Feng Wang
Haimin Chen
Wei Wu
author_sort Min Tang
collection DOAJ
description Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.
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spelling doaj.art-d2e9baa839664515821ed9ac4748718e2023-11-17T23:28:22ZengMDPI AGNutrients2072-66432023-04-01159204410.3390/nu15092044The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by ImmunomodulationMin Tang0Leilei Zhai1Juanjuan Chen2Feng Wang3Haimin Chen4Wei Wu5State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo 315211, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo 315211, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo 315211, ChinaDepartment of Laboratory Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo 315040, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo 315211, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo 315211, ChinaGastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.https://www.mdpi.com/2072-6643/15/9/2044λ-carrageenan oligosaccharidesgastric carcinomaPar-4 signaling pathwayimmunoregulation
spellingShingle Min Tang
Leilei Zhai
Juanjuan Chen
Feng Wang
Haimin Chen
Wei Wu
The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
Nutrients
λ-carrageenan oligosaccharides
gastric carcinoma
Par-4 signaling pathway
immunoregulation
title The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
title_full The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
title_fullStr The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
title_full_unstemmed The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
title_short The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation
title_sort antitumor potential of λ carrageenan oligosaccharides on gastric carcinoma by immunomodulation
topic λ-carrageenan oligosaccharides
gastric carcinoma
Par-4 signaling pathway
immunoregulation
url https://www.mdpi.com/2072-6643/15/9/2044
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