Proteome Analysis of Camellia nitidissima Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway

Chen, Yiwei; Zhang, Fan; Du, Zhenhong; Xie, Jinling; Xia, L.; Hou, Xin; Hao, Erhong; Deng, Jiagang

doi:10.3389/fonc.2021.727130

Cited by 20 publications

(10 citation statements)

References 36 publications

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“…We first assessed the effect of GA on the proliferation of HCC1806 cells by MTT and plate clone formation assays. The results showed that GA could inhibit HCC1806 cells proliferation in a dose-and time-dependent manner ( Zeng et al, 2020 ; Chen et al, 2021 ). Meanwhile, we found that the morphology of HCC1806 cells changed significantly after GA treatment, the number of HCC1806 cells decreased and the cells were in an apoptotic state.…”

Section: Discussionmentioning

confidence: 99%

Gallic acid suppresses the progression of triple-negative breast cancer HCC1806 cells via modulating PI3K/AKT/EGFR and MAPK signaling pathways

Lin

Qin

et al. 2022

Front. Pharmacol.

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Triple-negative breast cancer (TNBC) is a severe threat to women’s health because of its aggressive nature, early age of onset, and high recurrence rate. Therefore, in this study, we aimed to evaluate the anti-tumor effects of Gallic acid (GA) on the TNBC HCC1806 cells in vitro. The cell proliferation was detected by MTT and plate clone formation assays, cell apoptosis, cell cycle, and mitochondrial membrane potential (MMP) were analyzed by flow cytometry and Hoechst 33258 staining assays, and the intracellular reactive oxygen species (ROS) accumulation were also investigated. Real-Time PCR and western blot were examined to explore the mechanism of action. The results indicated that GA suppressed HCC1806 cells proliferation and promoted HCC1806 cells apoptosis. Meanwhile, GA treatment changed the morphology of the HCC1806 cells. In addition, GA blocked the HCC1806 cells cycle in the S phase, and it induced cells apoptosis accompanied by ROS accumulation and MMP depolarization. Real-Time PCR results suggested that GA increased Bax, Caspase-3, Caspase-9, P53, JINK and P38 mRNA expression, and decreased Bcl-2, PI3K, AKT and EGFR mRNA expression. Western blotting results suggested that GA increased Bax, cleaved-Caspase-3, cleaved-Caspase-9, P53, P-ERK1/2, P-JNK, P-P38 proteins expression, and decreased Bcl-2, P-PI3K, P-AKT, P-EGFR proteins expression. Furthermore, molecular docking suggested that GA has the high affinity for PI3K, AKT, EGFR, ERK1/2, JNK, and P38. In conclusion, GA could suppress HCC1806 cells proliferation and promote HCC1806 cells apoptosis through the mitochondrial apoptosis pathway and induces ROS generation which further inhibits PI3K/AKT/EGFR and activates MAPK signaling pathways. Our study will provide some new references for using GA in the treatment of TNBC.

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Section: Discussionmentioning

confidence: 99%

Gallic acid suppresses the progression of triple-negative breast cancer HCC1806 cells via modulating PI3K/AKT/EGFR and MAPK signaling pathways

Lin

Qin

et al. 2022

Front. Pharmacol.

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“…The key event in ferroptosis is cell membrane damage associated with peroxidation of lipids (24). GPX4, which is an antioxidant enzyme that reduces ROS, can prevent the formation of toxic lipid peroxides (17,21). Inhibition of GPX4 activity results in ferroptotic cell death.…”

Section: Elevated Gpx4 and Ferrous Iron Are Potential Therapeutic Tar...mentioning

confidence: 99%

“…Iron accumulation, particularly ferrous iron (Fe 2+ ), can create ROS by participating in the Fenton reaction, thereby triggering ferroptosis (18). Additionally, the lipid ROS scavenger gutathione peroxidase 4 (GPX4) can convert lipid peroxides into non-toxic lipid alcohols to protect cells against ferroptotic death (19)(20)(21). Drug-tolerant persister breast cancer cells are vulnerable to ferroptosis induced by GPX4 inhibition (16).…”

Section: Introductionmentioning

confidence: 99%

Glutathione Peroxidase 4 as a Therapeutic Target for Anti-Colorectal Cancer Drug-Tolerant Persister Cells

Zhang

Ma²,

Yang³

et al. 2022

Front. Oncol.

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BackgroundDespite the effectiveness of chemotherapy and targeted therapy for colorectal cancer, drug resistance drives therapy failure and tumor relapse. Increasing evidence has suggested that cancer cells can enter a reversible drug-tolerant persister state to survive chemotherapy or targeted agents. However, the traits and treatable vulnerabilities of anti-colorectal cancer drug-tolerant persister cells is not yet known.MethodsIn this study, we established 5-fluorouracil and AZ628-tolerant persister cell models in two colorectal cancer cell lines, namely HCT116 and SW620, and revealed the characteristics of colorectal cancer persister cells by cell viability assay and flow cytometry. We investigated the efficacy and mechanism of ferroptosis inducers RSL3 and FIN56 on persister cells, which are glutathione peroxidase 4 inhibitors. In the xenograft mouse model, we further evaluated the inhibitory effect of RSL3 on tumor regrowth.ResultsColorectal cancer persister cells, which were enriched in the residual cancer cell population, exhibited reduced drug sensitivity, were largely quiescent and expressed high levels of stem cell-related genes and mesenchymal markers but not epithelial markers. The persister cells were more sensitive and underwent ferroptosis induced by glutathione peroxidase 4 inhibitors. Mechanistically, glutathione peroxidase 4 and ferrous iron, which are pivotal ferroptosis regulators, were upregulated in residual cells or tumors, and were hence potential therapeutic targets of persister cells. In the xenograft model, we confirmed that inhibition of glutathione peroxidase 4 restrained tumor regrowth after discontinuation of anti-cancer drug treatment. Moreover, biopsies obtained from patients with colorectal cancer undergoing neoadjuvant chemoradiotherapy revealed upregulated glutathione peroxidase 4 and ferritin heavy chain 1. High glutathione peroxidase 4 expression correlates with a worse prognosis in colorectal cancer patients.ConclusionsOur work reveals that the upregulated glutathione peroxidase 4 and ferrous iron in anti-colorectal cancer drug-tolerant persister cells were potential therapeutic targets. Glutathione peroxidase 4 inhibition combined with chemotherapy or targeted therapy may be a promising therapy for colorectal cancer.

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“…Further mechanistic studies using proteomic and functional clustering analyses showed that AUCAN treatment upregulated 24 proteins and downregulated 42 proteins, suggesting that AUCAN treatment may regulate multiple genes in CRC. Chen et al (2021)conducted a label-free based quantitative proteomic analysis to evaluate the protein expression profiles in colon cancer cells treated with the traditional Chinese medicine Camellia nitidissima Chi (CNC). They showed that CNC regulated CRC cell proliferation via regulation of ferroptosis signaling.…”

Section: Proteomicsmentioning

confidence: 99%

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers

Wang

et al. 2022

Front. Pharmacol.

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Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.

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Proteome Analysis of Camellia nitidissima Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway

Cited by 20 publications

References 36 publications

Gallic acid suppresses the progression of triple-negative breast cancer HCC1806 cells via modulating PI3K/AKT/EGFR and MAPK signaling pathways

Gallic acid suppresses the progression of triple-negative breast cancer HCC1806 cells via modulating PI3K/AKT/EGFR and MAPK signaling pathways

Glutathione Peroxidase 4 as a Therapeutic Target for Anti-Colorectal Cancer Drug-Tolerant Persister Cells

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers

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