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Curcumin reverses irinotecan-acquired resistance in colorectal cancer cells: insights from whole transcriptomic data

ABSTRACT: Curcumin reverses irinotecan-acquired resistance in colorectal cancer cells: insights from whole transcriptomic data

PROVIDER: PRJNA1216903 | ENA |

REPOSITORIES: ENA

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Curcumin reverses irinotecan-acquired resistance in colorectal cancer cells: insights from whole transcriptomic data

Project description:To investigate the key mechanisms underlying the acquisition of irinotecan resistance in colorectal cancer cells and the reversal of this resistance by curcumin, we utilized whole-genome microarray expression profiling as a discovery tool to identify the signaling networks involved. Resistance acquisition led to dysregulation of genes associated with irinotecan resistance, including TOP1, drug-metabolizing enzymes (CYPs and UGTs), and efflux transporters (ABCs), while also affecting the extression of 53 genes involed in proliferation and 33 in cell motility. Curcumin treatment significantly modulated 3,901 genes (FC >|±2|), inducing apoptosis, reducing proliferation, and inhibiting migration. Curcumin also enhanced sensitivity to irinotecan, by upregulating TOP1 and inhibiting 18 CYPs, 4 UGTs, and 20 ABCs, including those upregulated in irinotecan-resistant cells.

2025-02-03 | GSE288308 | GEO

Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-kB signaling pathway

Project description:Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. The NF-kBsignalling pathway deregulation has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-kBwas hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-kB inhibitor. The concomitant combination of Curcumin+OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion oftheir resistant phenotype, through the inhibition of the NF-kBsignalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-KB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells thatwere more efficiently down-regulated after OXA+Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-kBpathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastaseswas associated with response to OXA+Curcumin.In conclusion, we suggest that combination of OXA+Curcumincould be an effective treatment in CRC patients after progression to OXA-based chemotherapy being CXCL1a good candidate predictive marker to this treatment.

2016-12-07 | GSE76092 | GEO

Mechanistic insights into anti-cancer properties of Curcumin and Andrographis in colorectal cancer

Project description:Colorectal cancer (CRC) remains the major leading cause of cancer-related deaths worldwide. The limitations of current chemotherapeutic drugs in CRC include their toxicity, side effects, and exorbitant costs. To assess these unmet needs in CRC treatment, several naturally occurring compounds, including Curcumin and Andrographis, have gained increasing attention due to their multi-targeted functionality and safety vs. conventional drugs. In the current study, we revealed that a combination of Curcumin and Andrographis exhibited superior anti-tumor effects by inhibiting cell proliferation, invasion, colony formation, and induction of apoptosis. Genomewide transcriptomic expression profiling analysis revealed that Curcumin and Andrographis activated the ferroptosis pathway.

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2010-09-29 | E-GEOD-23639 | biostudies-arrayexpress

Expression data from Irinotecan resistant LoVo cells comapred to parental LoVo cells

Project description:Irinotecan, an analogue of camptothecin, is frequently used in combination with various anticancer drugs or as a single agent in treatment of colorectal cancer. But drug resistance of tumor is still a major obstacle to overcome for the success of cancer treatment. In this study, We established chronic irinotecan resistant cell line for new marker to increase the sensitivity to irinotecan and investigated gene expression profiles of the irinotecan-resistant colorectal cancer cell line.

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Mechanistic insights into anti-cancer properties of Curcumin and Andrographis in colorectal cancer

Project description:Mechanistic insights into anti-cancer properties of Curcumin and Andrographis in colorectal cancer

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Effect of Curcumin on Dose Limiting Toxicity and Pharmacokinetics of Irinotecan in Patients With Solid Tumors

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Transcription profiling of topoisomerase I inhibitor irinotecan (CPT-11) sensitive, resistant, and reverted human neuroblastomas

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