Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets

Zhong, Zhangfeng; Vong, Chi Teng; Chen, Feiyu; Tan, Hor‐Yue; Zhang, Cheng; Wang, Ning; Cui, Liao; Wang, Yitao; Feng, Yibin

doi:10.1002/med.21876

Cited by 46 publications

(29 citation statements)

References 183 publications

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“…Table 1 collects immunomodulatory natural products with antitumor properties de- Although the field of immunotherapy is still growing, the discovery of immunomodulatory NPs able to stimulate the innate immunity cells represent the new frontier for tumor therapy. Zhong et al have recently reviewed natural products from herbal medicines with immunomodulatory potential as immune checkpoints inhibitors [14]. Other studies have demonstrated that also some conventional chemotherapeutic agents can also affect the immune system by different mechanisms.…”

Section: Terrestrial Environmentmentioning

confidence: 99%

Antitumor Potential of Immunomodulatory Natural Products

Nuzzo¹,

Senese²,

Gallo³

et al. 2022

Marine Drugs

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Cancer is one of the leading causes of death globally. Anticancer drugs aim to block tumor growth by killing cancerous cells in order to prevent tumor progression and metastasis. Efficient anticancer drugs should also minimize general toxicity towards organs and healthy cells. Tumor growth can also be successfully restrained by targeting and modulating immune response. Cancer immunotherapy is assuming a growing relevance in the fight against cancer and has recently aroused much interest for its wider safety and the capability to complement conventional chemotherapeutic approaches. Natural products are a traditional source of molecules with relevant potential in the pharmacological field. The huge structural diversity of metabolites with low molecular weight (small molecules) from terrestrial and marine organisms has provided lead compounds for the discovery of many modern anticancer drugs. Many natural products combine chemo-protective and immunomodulant activity, thus offering the potential to be used alone or in association with conventional cancer therapy. In this review, we report the natural products known to possess antitumor properties by interaction with immune system, as well as discuss the possible immunomodulatory mechanisms of these molecules.

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Section: Terrestrial Environmentmentioning

confidence: 99%

Antitumor Potential of Immunomodulatory Natural Products

Nuzzo¹,

Senese²,

Gallo³

et al. 2022

Marine Drugs

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“…Phytochemicals may illustrate their antitumor properties through promoting apoptosis, suppressing the cell cycle, inhibiting angiogenesis and regulating antioxidant activities. Moreover, numerous naturally bioactive compounds have been shown to modulate immune checkpoints and affect the activities of immune cells including T and B cells, Treg cells and NK cells [ 8 ]. More interestingly, these natural products have gained competing interests due to the absence of toxicity and harmful side effects commonly associated with current therapies [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Exploration of the genes with abnormal expression during the treatment of colon cancer with Gemini-Cur is essential to provide a deeper understanding of the mechanisms involved. Because regulatory genes are affected by dietary compounds, the ability of curcumin to modulate the transcriptome profile has attracted much attention [ 8 , 17 ]. Based on our recent findings on the significant toxic properties of Gemini-Cur on cancer cells, here, we employed RNA sequencing and bioinformatics analysis to identify the key genes and related pathways modulated in colorectal HCT-116 cells treated with Gemini-Cur.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin

Azeez

Neri²,

Feizi³

et al. 2022

Molecules

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Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. The gemini nanoparticle formulation of polyphenolic curcumin significantly inhibits the viability of cancer cells. However, the molecular mechanisms and pathways underlying its toxicity in colon cancer are unclear. Here, we aimed to uncover the possible novel targets of gemini curcumin (Gemini-Cur) on colorectal cancer and related cellular pathways. After confirming the cytotoxic effect of Gemini-Cur by MTT and apoptotic assays, RNA sequencing was employed to identify differentially expressed genes (DEGs) in HCT-116 cells. On a total of 3892 DEGs (padj < 0.01), 442 genes showed a log2 FC >|2| (including 244 upregulated and 198 downregulated). Gene ontology (GO) enrichment analysis was performed. Protein–protein interaction (PPI) and gene-pathway networks were constructed by using STRING and Cytoscape. The pathway analysis showed that Gemini-Cur predominantly modulates pathways related to the cell cycle. The gene network analysis revealed five central genes, namely GADD45G, ATF3, BUB1B, CCNA2 and CDK1. Real-time PCR and Western blotting analysis confirmed the significant modulation of these genes in Gemini-Cur-treated compared to non-treated cells. In conclusion, RNA sequencing revealed novel potential targets of curcumin on cancer cells. Further studies are required to elucidate the molecular mechanism of action of Gemini-Cur regarding the modulation of the expression of hub genes.

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“…Previously studies have demonstrated that several naturally bioactive compounds isolated from herbal medicines can modulate immune checkpoints in tumors ( Liu Y. et al, 2020 ; Yin et al, 2020 ). Besides, multiple natural products modulate the TME by regulating the activities of several types of immune cells, including T lymphocytes, B lymphocytes, Tregs, DCs, and NK cells, thereby exert anti-tumor function ( Sellam et al, 2020 ; Jiang et al, 2021 ; Zhong et al, 2022 ). However, in clinical treatment, the use of natural products is limited due to individual differences in patients, tumor heterogeneity, TME differences and other characteristics.…”

Section: Discussionmentioning

confidence: 99%

Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment

et al. 2022

Front. Pharmacol.

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Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-β and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

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Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets

Cited by 46 publications

References 183 publications

Antitumor Potential of Immunomodulatory Natural Products

Antitumor Potential of Immunomodulatory Natural Products

Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin

Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment

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