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Resources » Paper

Rose F et al. (2024) Biomed Pharmacother "RNA is a pro-apoptotic target of cisplatin in cancer cell lines and C. elegans."

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  • Comments on Rose F et al. (2024) Biomed Pharmacother "RNA is a pro-apoptotic target of cisplatin in cancer cell lines and C. elegans." (0)

  • Overview

    PMID:
    38503239
    DOI:
    10.1016/j.biopha.2024.116450
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00066620

    Rose F, Koeberle B, Honnen S, Bay C, Burhenne J, Weiss J, Haefeli WE, & Theile D (2024). RNA is a pro-apoptotic target of cisplatin in cancer cell lines and C. elegans. Biomed Pharmacother, 173, 116450. doi:10.1016/j.biopha.2024.116450

    Cisplatin not only targets DNA but also RNA. However, it is largely unknown whether platinated RNA (Pt-RNA) causes apoptosis and thus contributes to the cytotoxic effects of cisplatin. Consequently, cellular RNA was isolated from HepG2 and LS180 cells, exposed to cisplatin, and the resulting Pt-RNA (20 ng Pt/µg RNA) was transfected into these cancer cell lines or used to treat an apoptosis reporter Caenorhabditis elegans (C. elegans) strain (MD701, expressing CED-1::GFP). Cellular and molecular effects of Pt-RNA were evaluated by luminogenic caspase 3/7 assays, PCR array analysis, and fluorescence microscopy-based quantification of apoptosis in C. elegans gonads. Assuming RNA cross-linking (pseudo double-stranded RNA), the contribution of the Toll-like receptor 3 (TLR3, a sensor of double-stranded RNA) to apoptosis induction in cancer cell lines was investigated by pharmacological TLR3 inhibition and overexpression. In contrast to controls, Pt-RNA significantly enhanced apoptosis in C. elegans (2-fold) and in the cancer cell lines (2-fold to 4-fold). TLR3 overexpression significantly enhanced the pro-apoptotic effects of Pt-RNA in HepG2 cells. TLR3 inhibition reduced the pro-apoptotic effects of Pt-RNA and cisplatin, but not of paclitaxel (off-target control). Gene expression analysis showed that Pt-RNA (but not RNA) significantly enhanced the mRNA levels of nuclear factor kappa B subunit 2 and interleukin-8 in HepG2 cells, suggesting that Pt-RNA is a damage-associated molecular pattern that additionally causes pro-inflammatory responses. Together, this data suggests that not only DNA but also cellular RNA is a functionally relevant target of cisplatin, leading to pro-apoptotic and immunogenic effects.

    Authors: Rose F, Koeberle B, Honnen S, Bay C, Burhenne J, Weiss J, Haefeli WE, Theile D


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