Etoposide Treatment of Cancer Cell Lines Results in Nuclear Localisation of Cleaved Gasdermin D

Soukaina Imlilss; Elif Eren

Makale detayları

Etoposide Treatment of Cancer Cell Lines Results in Nuclear Localisation of Cleaved Gasdermin D

Yazarlar:

Soukaina Imlilss | Elif Eren

Yayıncı:

Istanbul University

Ana Başlıklar:

Cancer Biology | Genotoxicity and Cytotoxicity

Dergi:

European Journal of Biology Vol.83 Issue 2, pp.204-212

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340835

pISSN:

2602-2575

Anahtar kelimeler:

Özet:

 Objective: Overcoming resistance to apoptosis is one of the main goals of cancer treatment. Subversion of apoptosis to pyroptosis, an inflammatory cell death mediated by Gasdermin family members, was previously proposed as an alternative strategy for killing cancer cells. Since the pyroptotic activity of Gasdermin D has been mainly studied in the context of inflammasome activation and its association with cancer is mostly based on expression correlation, we sought to determine whether Gasdermin D-mediated pyroptosis could be triggered in response to drugs used to induce apoptosis in cancer cells. Materials and Methods: Cancer cells were treated with different concentrations of etoposide, gemcitabine, and cisplatin, which are used as chemotherapeutic agents in various ongoing clinical trials. Membrane integrity was evaluated by measuring lactate dehydrogenase release, and Gasdermin D and Caspase activations and subcellular localisation of Gasdermin D were determined by western blotting. Results: Upon treatment with the well-known apoptosis inducer etoposide, a necrotic form of programmed cell death was observed in different cancer cell lines even at low drug concentrations. Additionally, cleavage analysis revealed a 20-kDa-Gasdermin D fragment in the supernatant of treated cells. Surprisingly, this cleaved form was localised in the nuclei of etoposide-treated cells rather than in the well-defined cytosolic and plasma membrane localisations. Conclusion: Overall, these results demonstrate the complex interplay between different cell death pathways and suggest that Gasdermin D generates a fragment presenting an unknown function in the nuclei of etoposide-treated cancer cell lines.

 Objective: Overcoming resistance to apoptosis is one of the main goals of cancer treatment. Subversion of apoptosis to pyroptosis, an inflammatory cell death mediated by Gasdermin family members, was previously proposed as an alternative strategy for killing cancer cells. Since the pyroptotic activity of Gasdermin D has been mainly studied in the context of inflammasome activation and its association with cancer is mostly based on expression correlation, we sought to determine whether Gasdermin D-mediated pyroptosis could be triggered in response to drugs used to induce apoptosis in cancer cells. Materials and Methods: Cancer cells were treated with different concentrations of etoposide, gemcitabine, and cisplatin, which are used as chemotherapeutic agents in various ongoing clinical trials. Membrane integrity was evaluated by measuring lactate dehydrogenase release, and Gasdermin D and Caspase activations and subcellular localisation of Gasdermin D were determined by western blotting. Results: Upon treatment with the well-known apoptosis inducer etoposide, a necrotic form of programmed cell death was observed in different cancer cell lines even at low drug concentrations. Additionally, cleavage analysis revealed a 20-kDa-Gasdermin D fragment in the supernatant of treated cells. Surprisingly, this cleaved form was localised in the nuclei of etoposide-treated cells rather than in the well-defined cytosolic and plasma membrane localisations. Conclusion: Overall, these results demonstrate the complex interplay between different cell death pathways and suggest that Gasdermin D generates a fragment presenting an unknown function in the nuclei of etoposide-treated cancer cell lines.

 Objective: Overcoming resistance to apoptosis is one of the main goals of cancer treatment. Subversion of apoptosis to pyroptosis, an inflammatory cell death mediated by Gasdermin family members, was previously proposed as an alternative strategy for killing cancer cells. Since the pyroptotic activity of Gasdermin D has been mainly studied in the context of inflammasome activation and its association with cancer is mostly based on expression correlation, we sought to determine whether Gasdermin D-mediated pyroptosis could be triggered in response to drugs used to induce apoptosis in cancer cells. Materials and Methods: Cancer cells were treated with different concentrations of etoposide, gemcitabine, and cisplatin, which are used as chemotherapeutic agents in various ongoing clinical trials. Membrane integrity was evaluated by measuring lactate dehydrogenase release, and Gasdermin D and Caspase activations and subcellular localisation of Gasdermin D were determined by western blotting. Results: Upon treatment with the well-known apoptosis inducer etoposide, a necrotic form of programmed cell death was observed in different cancer cell lines even at low drug concentrations. Additionally, cleavage analysis revealed a 20-kDa-Gasdermin D fragment in the supernatant of treated cells. Surprisingly, this cleaved form was localised in the nuclei of etoposide-treated cells rather than in the well-defined cytosolic and plasma membrane localisations. Conclusion: Overall, these results demonstrate the complex interplay between different cell death pathways and suggest that Gasdermin D generates a fragment presenting an unknown function in the nuclei of etoposide-treated cancer cell lines.

 Objective: Overcoming resistance to apoptosis is one of the main goals of cancer treatment. Subversion of apoptosis to pyroptosis, an inflammatory cell death mediated by Gasdermin family members, was previously proposed as an alternative strategy for killing cancer cells. Since the pyroptotic activity of Gasdermin D has been mainly studied in the context of inflammasome activation and its association with cancer is mostly based on expression correlation, we sought to determine whether Gasdermin D-mediated pyroptosis could be triggered in response to drugs used to induce apoptosis in cancer cells. Materials and Methods: Cancer cells were treated with different concentrations of etoposide, gemcitabine, and cisplatin, which are used as chemotherapeutic agents in various ongoing clinical trials. Membrane integrity was evaluated by measuring lactate dehydrogenase release, and Gasdermin D and Caspase activations and subcellular localisation of Gasdermin D were determined by western blotting. Results: Upon treatment with the well-known apoptosis inducer etoposide, a necrotic form of programmed cell death was observed in different cancer cell lines even at low drug concentrations. Additionally, cleavage analysis revealed a 20-kDa-Gasdermin D fragment in the supernatant of treated cells. Surprisingly, this cleaved form was localised in the nuclei of etoposide-treated cells rather than in the well-defined cytosolic and plasma membrane localisations. Conclusion: Overall, these results demonstrate the complex interplay between different cell death pathways and suggest that Gasdermin D generates a fragment presenting an unknown function in the nuclei of etoposide-treated cancer cell lines.

Makale detayları

Etoposide Treatment of Cancer Cell Lines Results in Nuclear Localisation of Cleaved Gasdermin D

Yazarlar:

Soukaina Imlilss | Elif Eren

Yayıncı:

Istanbul University

Ana Başlıklar:

Cancer Biology | Genotoxicity and Cytotoxicity

Dergi:

European Journal of Biology Vol.83 Issue 2, pp.204-212

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340835

pISSN:

2602-2575

Pyroptosis

Gasdermin D

Cancer

Etoposide

Nucleus

Sayı

Makale detayları

Etoposide Treatment of Cancer Cell Lines Results in Nuclear Localisation of Cleaved Gasdermin D

Yazarlar: Soukaina Imlilss | Elif Eren

Yayıncı: Istanbul University

Ana Başlıklar: Cancer Biology | Genotoxicity and Cytotoxicity

Dergi: European Journal of Biology Vol.83 Issue 2, pp.204-212

Belge Tipi: Makale

Yayın Tarihi: 12/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001340835

pISSN: 2602-2575

Pyroptosis

Gasdermin D

Cancer

Etoposide

Nucleus

Sayı

Yazarlar:

Soukaina Imlilss | Elif Eren

Yayıncı:

Istanbul University

Ana Başlıklar:

Cancer Biology | Genotoxicity and Cytotoxicity

Dergi:

European Journal of Biology Vol.83 Issue 2, pp.204-212

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340835

pISSN:

2602-2575