MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis

Chan, David; Yung, Mingo M. H.; Chan, Yau-Sang; Yang, Xuan; Yang, Huijuan; Xu, Dakang; Zhan, Jun; Chan, Karen Kl; Ng, T.B.; Ngan, Hextan Ys

doi:10.1016/j.phrs.2020.105157

Cited by 87 publications

(49 citation statements)

References 47 publications

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“…Moreover, the median survival time of cluster 2 was shorter than cluster 1. Previous studies reported that MAP30 can prevent ovarian cancer progression through modulating ferroptosis [43]. Superparamagnetic iron oxide nanoparticles can induce ferroptosis to inhibit the progression of ovarian cancer stem cells [44].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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“…Since the ESTIMATE algorithm cannot precisely distinguish patients with OC with high-risk well, we decided to introduce FRGs into the prognostic risk prediction model for OC. Recently reported FRGs are associated with platinum resistance and poor prognosis in OC, while ferroptosis could affect the activation and function of immune cells ( Friedmann Angeli et al, 2019 ; CHAN et al, 2020 ; WANG et al, 2021 ; MA et al, 2021 ). It could be inferred that the integration of the immune and FRGs may be able to assess the condition of OC patients and form an effective prognostic predictive risk model.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of the Tumor Microenvironment and Ferroptosis-Related Genes Predict Prognosis with Ovarian Cancer

Wen

et al. 2021

Front. Genet.

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The early diagnosis of ovarian cancer (OC) is critical to improve the prognosis and prevent recurrence of patients. Nevertheless, there is still a lack of factors which can accurately predict it. In this study, we focused on the interaction of immune infiltration and ferroptosis and selected the ESTIMATE algorithm and 15 ferroptosis-related genes (FRGs) to construct a novel E-FRG scoring model for predicting overall survival of OC patients. The gene expression and corresponding clinical characteristics were obtained from the TCGA dataset (n = 375), GSE18520 (n = 53), and GSE32062 (n = 260). A total of 15 FRGs derived from FerrDb with the immune score and stromal score were identified in the prognostic model by using least absolute shrinkage and selection operator (LASSO)–penalized COX regression analysis. The Kaplan–Meier survival analysis and time-dependent ROC curves performed a powerful prognostic ability of the E-FRG model via multi-validation. Gene Set Enrichment Analysis and Gene Set Variation Analysis elucidate multiple potential pathways between the high and low E-FRG score group. Finally, the proteins of different genes in the model were verified in drug-resistant and non–drug-resistant tumor tissues. The results of this research provide new prospects in the role of immune infiltration and ferroptosis as a helpful tool to predict the outcome of OC patients.

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“…Meanwhile, MAP30 has been found in BMEVs. MAP30 could increase the intracellular Ca 2+ ion concentration, which triggered ROS-mediated cancer cell death via apoptosis [ 30 ]. In our study, we observed the generation of ROS after BMEVs treatment, which may mediate by MAP30 protein in BMEVs.…”

Section: Discussionmentioning

confidence: 99%

Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma

Yang

Luo

et al. 2021

J Nanobiotechnol

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Background Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU. Results Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N-acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU. Conclusions Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy. Graphic Abstract

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MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis

Cited by 87 publications

References 47 publications

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Comprehensive Analysis of the Tumor Microenvironment and Ferroptosis-Related Genes Predict Prognosis with Ovarian Cancer

Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma

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