Mechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells

Basit Öğe Kaydı
dc.authoridJoha, Ziad/0000-0001-8520-3760
dc.authoridErgul, Mustafa/0000-0003-4303-2996
dc.contributor.authorYulak, Fatih
dc.contributor.authorFiliz, Ahmet Kemal
dc.contributor.authorJoha, Ziad
dc.contributor.authorErgul, Mustafa
dc.date.accessioned2024-10-26T18:05:49Z
dc.date.available2024-10-26T18:05:49Z
dc.date.issued2023
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractThe PI3K pathway plays a crucial role in tumor cell proliferation across various cancers, including colon cancer, making it a promising treatment target. This study aims to investigate the antiproliferative activity of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor, on colon cancer and elucidate the underlying mechanisms. HT-29 colon cancer cells were treated with varying doses of ETP 45658 and its cytotoxic effect assessed using the XTT cell viability assay.ELISA was also used to measure TAS, TOS, Bax, BCL-2, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels. Flow cytometry was performed to investigate apoptosis, cell cycle, caspase 3/7 activity, and mitochondrial membrane potential. Additionally, following the administration of DAPI (4,6-diamidino-2-phenylindole) dye, the cells were visualized using an immunofluorescence microscope. It was observed that ETP-45658 exerted a dose-dependent and statistically significant antiproliferative effect on HT-29 colon cancer cells. Further investigations using the IC50 dose showed that ETP-45658 decreased TAS levels and increased TOS levels and revealed that it upregulated apoptotic proteins while downregulating anti-apoptotic proteins. Our findings also showed that it increased Annexin V binding, arrested the cell cycle at G0/G1 phase, induced caspase 3/7 activity, impaired mitochondrial membrane potential, and ultimately triggered apoptosis in HT-29 cells. ETP-45658 shows promise against colon cancer by inducing cell death, and oxidative stress, and arresting the cell cycle. Targeting the PI3K/AKT/mTOR pathway with ETP-45658 offers exciting potential for colon cancer treatment.
dc.description.sponsorshipThe authors express their gratitude to the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the essential resources and facilities required for the successful execution of this study.
dc.description.sponsorshipThe authors express their gratitude to the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the essential resources and facilities required for the successful execution of this study.
dc.identifier.doi10.1007/s12032-023-02221-4
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue12
dc.identifier.pmid37891359
dc.identifier.scopus2-s2.0-85175014105
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s12032-023-02221-4
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29203
dc.identifier.volume40
dc.identifier.wosWOS:001088529200002
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherHumana Press Inc
dc.relation.ispartofMedical Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAnticancer
dc.subjectPI3K/AKT/mTOR inhibition
dc.subjectETP-45658
dc.subjectCell cycle
dc.subjectApoptosis
dc.titleMechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksyonu
Scopus İndeksli Yayınlar Koleksiyonu