Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

Zhou, Xuebing; Yang, Chunyu; Li, Yuan; Chen, Dan; Wang, Tong; Liu, Tesi; Yan, Wendi; Su, Zhaoxia; Peng, Bosen; Ren, Xiangshan

doi:10.1016/j.lfs.2023.121698

Cited by 8 publications

(2 citation statements)

References 39 publications

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“…The current study also confirmed that cordycepin markedly suppresses the migratory ability of SNU478 cells, which is partly associated with the sensitization of CCA cells to gemcitabine. Cordycepin has been reported to suppress metastasis and EMT in CCA by regulating lipid metabolism ( Zhou et al ., 2023 ). Therefore, our results support a possible role of cordycepin in the relationship between EMT and the cancer stem-like properties in CCA.…”

Section: Discussionmentioning

confidence: 99%

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Lee,

Na,

Seong

et al. 2024

Biomol Ther (Seoul)

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Cordycepin, a valuable bioactive component isolated from Cordyceps militaris , has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine co-treatment reduced the CD44 high CD133 high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2–related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

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Section: Discussionmentioning

confidence: 99%

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Lee,

Na,

Seong

et al. 2024

Biomol Ther (Seoul)

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“…After processing, a mature form of SREBP-1 translocates into the nucleus to stimulate transcription of its target genes, including those encoding key enzymes of the adipogenic pathway (e.g., ACLY, ACCAA, FASN, and SCD) [ 43 ]. eRO1A promotes migration and lipid metabolism in CCA cells through the AKT/mTOR/SREBP-1 signaling pathway [ 44 ]. EGFR, a tyrosine kinase receptor of the ErbB receptor family, activates PI3K/AKT in response to EGF stimulation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing

Huang,

Cao,

Liu

et al. 2024

Cell Death Dis

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Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive cancer characterized by a poor prognosis and resistance to chemotherapy. In this study, utilizing scRNA-seq, we discovered that the tetra-transmembrane protein mal, T cell differentiation protein 2 (MAL2), exhibited specific enrichment in ICC cancer cells and was strongly associated with a poor prognosis. The inhibition of MAL2 effectively suppressed cell proliferation, invasion, and migration. Transcriptomics and metabolomics analyses suggested that MAL2 promoted lipid accumulation in ICC by stabilizing EGFR membrane localization and activated the PI3K/AKT/SREBP-1 axis. Molecular docking and Co-IP proved that MAL2 interacted directly with EGFR. Based on constructed ICC organoids, the downregulation of MAL2 enhanced apoptosis and sensitized ICC cells to cisplatin. Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC.

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Insights into the methods for separation and chromatographic determination of nucleotides/nucleosides in Cordyceps spp.

Peng,

Li,

Tong

2024

Journal of Chromatography A

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Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

Cited by 8 publications

References 39 publications

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing

Insights into the methods for separation and chromatographic determination of nucleotides/nucleosides in Cordyceps spp.

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