Chemo-sensitive and chemo-resistant ovarian cancer cells show differences in cellular processes leading to pyroptotic cell death        
Yazarlar (3)
Dr. Öğr. Üyesi Çağlar BERKEL Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Aysun Keskin
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Prof. Dr. Ercan ÇAÇAN Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı Pathology Research and Practice
Dergi ISSN 1618-0631 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 05-2025
Cilt No 269
Sayı 1
Sayfalar 155911 / 0
DOI Numarası 10.1016/j.prp.2025.155911
Makale Linki https://doi.org/10.1016/j.prp.2025.155911
Özet
Tumor immunology in ovarian cancer is not completely understood. Chemoresistance limits the success of available treatment options for patients with ovarian cancer. Pyroptosis, pro-inflammatory programmed cell death characterized by membrane pore formation by gasdermin proteins, is important for both immunogenicity and drug resistance. Here, we showed that estrogen increases GSDMC and GSDMD mRNA levels in chemo-sensitive ovarian cancer cells; but, not in chemo-resistant ovarian cancer cells in vitro. GSDMC or GSDMD overexpression increases cell viability in chemo-sensitive ovarian cancer cells; but, not in chemo-resistant ovarian cancer cells. Silencing of GSDMD in chemo-sensitive ovarian cancer cells and silencing of GSDMC in chemo-resistant ovarian cancer cells limit the effect of nigericin, a pyroptosis inducer, on cell viability. Inhibition of caspase-1, -4, -6 or -8 blocks nigericin-induced cell death (pyroptosis) in chemo-sensitive ovarian cancer cells; however, only the inhibition of caspase-1 blocks nigericin-induced cell death in chemo-resistant ovarian cancer cells, showing that caspases participating in pyroptosis might differ between ovarian cancer cells based on their chemo-sensitivity profiles. Treatment with disulfiram, a GSDMD pore formation inhibitor, decreases cell viability in both cell lines. Lastly, we found that in chemo-resistant ovarian cancer cell line, disulfiram and nigericin combination treatment decreases cell viability even more compared to only disulfiram or only nigericin treatment. Combined, our study points that ovarian cancer cells with different chemosensitivity profiles might have certain differences in pyroptotic cell death.
Anahtar Kelimeler
Cell death | Chemoresistance | Chemosensitivity | Disulfiram | Drug resistance | Estrogen | GSDMC | GSDMD | Inflammation | Nigericin | Ovarian cancer | Pyroptosis