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Elevated level of neuroserpin is an indication for the resistance to gambogic acid-induced apoptosis and oxidative stress in triple-negative breast cancer cells   
Yazarlar
Ertan Küçüksayan
Alanya Alaaddin Keykubat Üniversitesi, Türkiye
Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN
Kastamonu Üniversitesi, Türkiye
Mehmet Enes Sözen
Türkiye
Aslınur Sırcan Küçüksayan
Alanya Alaaddin Keykubat Üniversitesi, Türkiye
Özet
Background: The triple-negative breast cancer (TNBC) subtype, characterized by loss of HER2, estrogen, and progesterone receptors, displays aggressive phenotype and poor prognosis compared to other BC subtypes. Since the TNBC cells are devoid of receptors, endocrine therapy is an ineffective option for TNBC patients, necessitating canonical chemotherapy strategies to treat TNBC. It is crucial to use alternative and natural agents to support chemotherapy in TNBC. Objectives: To clarify the molecular mechanism of the tumorigenic effects of gambogic acid (GA) on TNBC cells with different epithelial character since GA has a wide spectrum of anticancer activity for most cancer types. Methods: We determined the cytotoxic dose of GA incubation of TNBC cells (MDA-MB-231 and BT-20 cells) for 24 h. We performed the MTT test and toluidine blue (TB) staining protocol for TNBC cells. We analyzed E-cadherin, N-cadherin, Bax, and neuroserpin mRNAs in both cells by qPCR. We evaluated apoptosis using DAPI staining and assessed the ROS using the 2',7'-dichlorofluorescin diacetate (DCFH-DA) method. Results: We determined the IC50 concentrations of GA in MDA-MB-231 and BT-20 cells to be 315.8 nM and 441.8 nM, respectively. TB staining showed that BT-20 cells survive at excessive cytotoxic doses of GA, while most of the MDA-MB-231 cells were killed. Also, we found that BT-20 cells are more resistant to GA-induced apoptosis and oxidative stress than the MDA-MB-231 cells. qPCR results showed that GA upregulated neuroserpin, an oxidative stress-relieving factor in the BT-20 cells, but not in the MDA-MB-231 cells. Conclusions: The elevated level of neuroserpin could be a predictive marker to determine the development of resistance to chemotherapeutic agents.
Anahtar Kelimeler
apoptosis | gambogic acid | neuroserpin | oxidative stress | triple-negative breast cancer
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Asian Biomedicine
Dergi ISSN 1875-855X
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q4
Makale Dili İngilizce
Basım Tarihi 01-2024
Cilt No 18
Sayı 2
Sayfalar 69 / 80
Doi Numarası 10.2478/abm-2024-0010
Makale Linki http://dx.doi.org/10.2478/abm-2024-0010