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 |