Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents

Liu, Qiuping; Chen, Yuying; An, Peng; Rahman, Khalid; Luan, Xin; Zhang, Hong

doi:10.1016/j.phymed.2022.154612

Cited by 6 publications

(3 citation statements)

References 102 publications

(92 reference statements)

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“…Natural products have garnered increasing attention as potential adjunctive anti-tumor therapies in preclinical and clinical trials for their minimal toxicity, restricted side effects, and favorable tolerance properties [ 38 ]. Of note, they also regulate cytokine secretion and the expression of cell surface molecules, which contribute to maintain a balanced tumor microenvironment, especially by influencing the activation and polarization of macrophages [ 39 ]. 23-HBA is an effective active ingredient derived from the dried root of P. chinensis , known for its well-established anti-tumor effects.…”

Section: Discussionmentioning

confidence: 99%

23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling

Fan,

Cui,

Chen

et al. 2024

Cancer Immunol Immunother

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Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of Pulsatilla chinensis (P. chinensis), to inhibit the polarization of M2 macrophages induced by IL-4. Our results showed that 23-HBA reduced the expression of M2 specific marker CD206, while downregulating the mRNA levels of M2 related genes (CD206, Arg1, IL-10, and CCL2). Additionally, 23-HBA effectively attenuated the inhibitory effects of the conditioned medium from M2 macrophages on apoptosis in colorectal cancer SW480 cells. Mechanistically, 23-HBA prevented the phosphorylation and nuclear translocation of the STAT6 protein, resulting in the inhibition of IL-10 release in M2 macrophages. Moreover, it interfered with the activation of the IL-10/STAT3/Bcl-2 signaling pathway in SW480 cells, ultimately reducing M2 macrophage-induced resistance to 5-FU. Importantly, depleting STAT6 expression in macrophages abolished the suppressive effect of 23-HBA on M2 macrophage polarization, while also eliminating its ability to decrease M2 macrophage-induced 5-FU resistance in cancer cells. Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling

Fan,

Cui,

Chen

et al. 2024

Cancer Immunol Immunother

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“…Plants are considered to be important sources of substances for the treatment of cancer, being effective, safe, and with structures subject to modification. Natural products have antioxidant, growth-inhibiting, apoptosis-inducing, and invasion-and metastasiscontrol activities [204][205][206]. Despite advances in scientific studies focused on this area, it is estimated that only 15% of existing plant species have already been investigated for their pharmacological potential [207].…”

Section: Natural Compounds and Their Effects On Luminal Tumorsmentioning

confidence: 99%

Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer

da Silva,

Brandão,

Ferreira

et al. 2023

Pharmaceuticals

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Breast cancer (BC) is the most diagnosed cancer worldwide, mainly affecting the epithelial cells from the mammary glands. When it expresses the estrogen receptor (ER), the tumor is called luminal BC, which is eligible for endocrine therapy with hormone signaling blockade. Hormone therapy is essential for the survival of patients, but therapeutic resistance has been shown to be worrying, significantly compromising the prognosis. In this context, the need to explore new compounds emerges, especially compounds of plant origin, since they are biologically active and particularly promising. Natural products are being continuously screened for treating cancer due to their chemical diversity, reduced toxicity, lower side effects, and low price. This review summarizes natural compounds for the treatment of luminal BC, emphasizing the activities of these compounds in ER-positive cells. Moreover, their potential as an alternative to endocrine resistance is explored, opening new opportunities for the design of optimized therapies.

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“…Natural polysaccharides (NPs) have various regulatory effects on macrophages, such as influencing the phenotype of macrophages [16]. Over the years, attention has been paid to the role of polysaccharides in resetting the phenotype of M2-like macrophages [17].…”

Section: Introductionmentioning

confidence: 99%

Dendrobium officinale polysaccharide Converts M2 into M1 Subtype Macrophage Polarization via the STAT6/PPAR-r and JAGGED1/NOTCH1 Signaling Pathways to Inhibit Gastric Cancer

Zhao,

Lu,

Huang

et al. 2023

Molecules

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Dendrobium officinale polysaccharide (DOP) has shown various biological activities. However, the ability of DOP to participate in immune regulation during anti-gastric cancer treatment has remained unclear. In this study, the in vitro results showed that DOP has the potential to polarize THP-1 macrophages from the M2 to the M1 phenotype, downregulate the STAT6/PPAR-r signaling pathway and the protein expression of their down-targeted ARG1 and TGM2, and further decrease the main protein and mRNA expression in the JAGGED1/NOTCH1 signaling pathway. DOP suppressed the migration of gastric cancer cells by decreasing the protein expression of N-cadherin and Vimentin and increasing E-cadherin. In addition, CM-DOP promoted the apoptosis of gastric cancer cells by upregulating Caspase-3 and increasing the ratio of Bax/Bcl-2. In vivo, DOP effectively inhibited the growth of tumors and the expression of Ki-67. In summary, these findings demonstrated that DOP converted the polarization of M2 subtype macrophages into M1 subtypes via the STAT6/PPAR-r and JAGGED1/NOTCH1 signaling pathways in order to reduce apoptosis and prevent migration, thus indicating the potential of DOP as an adjuvant tumor therapy in preclinical and clinical trials.

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Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents

Cited by 6 publications

References 102 publications

23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling

23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling

Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer

Dendrobium officinale polysaccharide Converts M2 into M1 Subtype Macrophage Polarization via the STAT6/PPAR-r and JAGGED1/NOTCH1 Signaling Pathways to Inhibit Gastric Cancer

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