Trichomicin Suppresses Colorectal Cancer via Comprehensive Regulation of IL-6 and TNFα in Tumor Cells, TAMs, and CAFs

Zhao, Xi; Qi, Xiaoqiang; Lian, Wenrui; Tong, Xin; Wang, Hua; Su, Liya; Wei, Ping; Zhuang, Zhuochen; Gong, Jianhua; Bai, Liping

doi:10.3389/fphar.2020.00386

Cited by 8 publications

(3 citation statements)

References 44 publications

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“…(4). CIS (MedChemExpress, Monmouth Junction, NJ, USA, 3 mg/kg, dissolved with 0.5% sodium carboxymethyl cellulose (CMC‐Na, MedChemExpress, Monmouth Junction, NJ, USA) according to manufacturer’s instructions) was administered twice a week for a total of five times 55 . (5).…”

Section: Methodsmentioning

confidence: 99%

Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment

et al. 2022

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Single-cell sequencing technologies have noteworthily improved our understanding of the genetic map and molecular characteristics of bladder cancer (BC). Here we identify CD39 as a potential therapeutic target for BC via single-cell transcriptome analysis. In a subcutaneous tumor model and orthotopic bladder cancer model, inhibition of CD39 (CD39i) by sodium polyoxotungstate is able to limit the growth of BC and improve the overall survival of tumor-bearing mice. Via single cell RNA sequencing, we find that CD39i increase the intratumor NK cells, conventional type 1 dendritic cells (cDC1) and CD8 + T cells and decrease the Treg abundance. The antitumor effect and reprogramming of the tumor microenvironment are blockaded in both the NK cells depletion model and the cDC1-deficient Batf3−/− model. In addition, a significant synergistic effect is observed between CD39i and cisplatin, but the CD39i + anti-PD-L1 (or anti-PD1) strategy does not show any synergistic effects in the BC model. Our results confirm that CD39 is a potential target for the immune therapy of BC.

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Section: Methodsmentioning

confidence: 99%

Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment

et al. 2022

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“…99 The macrophages within the tumor microenvironment also produce increased levels of antiangiogenic cytokines such as IL-6. 100 In order to understand the effects of MGF-AuNPs on macrophages, we have investigated the expression of macrophage polarizing cytokines such as IL-12, IL-10, IL-6, and TNF-α upon treating RAW 264.7 macrophages with MGF-AuNPs. In RAW 264.7 macrophages, which were treated with MGF-AuNPs, our experimental findings conclusively demonstrated elevated levels of anti-tumor cytokines such as IL-12 and TNF-, while reducing the levels of pro-tumor cytokines such as IL-10 and IL-6 (Figure 12A, D).…”

Section: Mgf-aunps But Not S-aunps Polarize Macrophages To Anti-tummentioning

confidence: 99%

Green Nanotechnology of MGF-AuNPs for Immunomodulatory Intervention in Prostate Cancer Therapy

Khoobchandani

Khan

Katti

et al. 2021

Preprint

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Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the differentiation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticles (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about fifty-fold; while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.

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“…Trichomicin is a small molecule compound with new structure isolated from Trichoderma harzianum ( T. harzianum ) in our laboratory ( Zhu et al, 2020 ). Early in vitro studies confirmed that Trichomicin has significant anti-inflammatory and anti-tumor activities, and inhibits the growth of colon tumor ( Qi et al, 2011 ; Zhao et al, 2020 ). Furthermore, our laboratory also used the anti-inflammatory model to screen the new structure small molecule compound 1487B.…”

Section: Introductionmentioning

confidence: 99%

Screening of Microbial Natural Products and Biological Evaluation of Trichomicin as Potential Anti-Cytokine Storm Agents

et al. 2021

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COVID-19 has remained an uncontained, worldwide pandemic. Most of the infected people had mild symptoms in the early stage, and suddenly worsened or even died in the later stage which made the cytokine release syndrome (CRS) once again aroused people’s attention. CRS is an excessive immunity of the body to external stimuli such as viruses, bacteria, and nanomaterials, which can cause tissue damage, local necrosis or even death. Lipopolysaccharide (LPS) is one of the most effective CRS inducers, which can activate macrophages to release cytokines, including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL- 6 and chemokines. We used RT-PCR to detect the expression of representative cytokines in mouse and human cells at different concentrations of Trichomicin, Ebosin, and 1487B after LPS stimulation. The results showed that the expression of TNF-α, IL-1β, IL-6, and CXCL10 all increased after LPS stimulation. Among the various drugs, Trichomicin had the most obvious inhibitory effect on cytokine expression in vitro, and it was further verified in vivo that Trichomicin can improve the survival rate of mice stimulated with LPS. Finally, it was proved that Trichomicin inhibited the Stat3 and NF-κB pathways and reduced the phosphorylation of Stat3 and p65 after LPS stimulation, thereby inhibiting the response of macrophages to pro-inflammatory stimuli. The article clarified the inhibitory activity and mechanism of action of Trichomicin on CRS, and laid the foundation for the research on the anti-cytokine storm activity of microbial natural products.

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Trichomicin Suppresses Colorectal Cancer via Comprehensive Regulation of IL-6 and TNFα in Tumor Cells, TAMs, and CAFs

Cited by 8 publications

References 44 publications

Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment

Single cell sequencing reveals that CD39 inhibition mediates changes to the tumor microenvironment

Green Nanotechnology of MGF-AuNPs for Immunomodulatory Intervention in Prostate Cancer Therapy

Screening of Microbial Natural Products and Biological Evaluation of Trichomicin as Potential Anti-Cytokine Storm Agents

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