β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer

Yu, Xiaomu; Xu, Mingxi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

doi:10.1016/j.bbrc.2017.06.071

Cited by 64 publications

(46 citation statements)

References 29 publications

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“…However, the molecular mechanism behind melittin inhibition awaits elucidation. It is possible that the M2 macrophages were reprogrammed to the M1 type (Yu et al, 2017), and so the expression of biomarkers for both M1 and M2 macrophages needs to be evaluated. Interestingly, ß-elemene, extracted from the Chinese herb Curcuma wenyujin, could induce the re-differentiation of M2 macrophages to the M1 type, where down-regulation of Arg-1 (M2 macrophage biomarker) and up-regulation of iNOS (M1 macrophage biomarker) was observed (Yu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Tipgomut

Wongprommoon

Takeo

et al. 2018

Asian Pac J Cancer Prev

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Background: Bronchogenic carcinoma (lung cancer) is one of the leading causes of death. Although many compounds isolated from natural products have been used to treat it, drug resistance is a serious problem, and alternative anti-cancer drugs are required. Here, melittin from Apis mellifera venom was used, and its effects on bronchogenic carcinoma cell proliferation and tumour-associated macrophage differentiation were evaluated. Methods: The half maximal inhibitory concentration (IC50) of melittin was measured by MTT. Cell death was observed by annexin V and propidium iodide (PI) co-staining followed by flow cytometry. Cell cycle arrest was revealed by PI staining and flow cytometry. To investigate the tumour microenvironment, differentiation of circulating monocytes (THP-1) into tumour-associated macrophages (TAMs) was assayed by sandwich-ELISA and interleukin (IL)-10 levels were determined. Cell proliferation and migration was observed by flat plate colony formation. Secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. The change in expression levels of CatS, Bcl-2, and MADD was measured by quantitative RT-PCR. Results: Melittin was significantly more cytotoxic (p < 0.01) to human bronchogenic carcinoma cells (ChaGo-K1) than to the control human lung fibroblasts (Wi-38) cells. At 2.5 µM, melittin caused ChaGo-K1 cells to undergo apoptosis and cell cycle arrest at the G1 phase. The IL-10 levels showed that melittin significantly inhibited the differentiation of THP-1 cells into TAMs (p < 0.05) and reduced the number of colonies formed in the treated ChaGo-K1 cells compared to the untreated cells. However, melittin did not affect angiogenesis in ChaGo-K1 cells. Unlike MADD, Bcl-2 was up-regulated significantly (p < 0.05) in melittin-treated ChaGo-K1 cells. Conclusion: Melittin can be used as an alternative agent for lung cancer treatment because of its cytotoxicity against ChaGo-K1 cells and the inhibition of differentiation of THP-1 cells into TAMs.

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Section: Discussionmentioning

confidence: 99%

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Tipgomut

Wongprommoon

Takeo

et al. 2018

Asian Pac J Cancer Prev

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“…The most common strategies for inflammation resolution dealing with M φ transformation is by promoting M2 and inhibiting M1 macrophage polarization, with the latter being more frequently used. The members of peroxisome proliferator-activated receptor (PPAR), interferon regulatory factor (IRF), signal transducers and activators of transcription (STAT), hypoxia inducible factor (HIF), nuclear factor-κB (NF-κB), and Kruppel-like transcription factor (KLF) families are now recognized as the major determinants of M1 and M2 polarization [51]. The following describes some advances in recent studies that are related to M1 and M2 polarization, along with the efficacy of some phytochemicals and nutraceuticals after intervention.…”

Section: Preventive and Therapeutic Strategies Dealing With M1/m2 mentioning

confidence: 99%

“…Therefore, unlike most circumstances in other diseases, M2 polarization inhibition has become a major strategy to retard cancer progression. β-elemene, an active component extracted from Curcuma Wenyujin , exhibited similar tumor-promoting effects in lung cancer by inhibiting migration, invasion transition of epithelial mesenchymal, concomitant with enhancing radiosensitivity of lung cancer cells [51]. Besides, Dong et al (2017) demonstrated the effect of fenretinide, a kind of synthetic derivative of all-trans retinoic acid on the inhibition of M2 macrophage polarization in colon cancer.…”

Section: Role Of Macrophages In Cancer Progressionmentioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

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Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

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“…A number of studies have found that TAMs are mostly M2-polarized, and it has been reported that these cells promote the growth and survival of tumors and may lead to resistance to cancer treatment [65]. β-Elemene not only decreases the proliferation, migration, and invasion and strengthens the radiosensitivity of lung cancer cells but also inhibits the promotion of migration, invasion, and EMT of lung cancer in M2 macrophageconditioned medium, regulating the polarization of macrophages from M2 to M1 [136]. Research shows that tumor cells in the irradiated or hypoxic microenvironment recruit macrophages and induce MCP-1 secretion, which leads to nuclear accumulation of NF-κB and HIF-1α.…”

Section: Effects Of β-Elemene On Macrophagesmentioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer

Cited by 64 publications

References 29 publications

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Melittin Induced G1 Cell Cycle Arrest and Apoptosis in Chago-K1 Human Bronchogenic Carcinoma Cells and Inhibited the Differentiation of THP-1 Cells into Tumour- Associated Macrophages

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

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