<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>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.</p>
</sec>
<sec><h3>Objectives</h3>
<p>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.</p>
</sec>
<sec><h3>Methods</h3>
<p>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 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) method.</p>
</sec>
<sec><h3>Results</h3>
<p>We determined the IC<sub>50</sub> 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.</p>
</sec>
<sec><h3>Conclusions</h3>
<p>The elevated level of neuroserpin could be a predictive marker to determine the development of resistance to chemotherapeutic agents.</p>
</sec>
</abstract>

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 2ʹ,7ʹ-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.

Elevated level of neuroserpin is an indication for the resistance to gambogic acid-induced apoptosis and oxidative stress in triple-negative breast cancer cells

Department of Medical Biochemistry, School of Medicine

Department of Medical Biology, School of Medicine

Department of Histology and Embryology, School of Medicine

Department of Biophysics, School of Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
The triple-negative breast cancer (TNBC) subtype, characterized by loss of HER2, estrogen, and progesterone receptors, displays aggressive phenotype...

Elevated level of neuroserpin is an indication for the resistance to gambogic acid-induced apoptosis and oxidative stress in triple-negative breast cancer cells

Article Category: Original article

Published Online: Apr 30, 2024

Page range: 69 - 80

DOI: https://doi.org/10.2478/abm-2024-0010

Keywords
apoptosis, gambogic acid, neuroserpin, oxidative stress, triple-negative breast cancer

© 2024 Ertan Kucuksayan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Elevated level of neuroserpin is an indication for the resistance to gambogic acid-induced apoptosis and oxidative stress in triple-negative breast cancer cells

Article Category: Original article

Published Online: Apr 30, 2024

Page range: 69 - 80

DOI: https://doi.org/10.2478/abm-2024-0010

Keywordsapoptosis, gambogic acid, neuroserpin, oxidative stress, triple-negative breast cancer

© 2024 Ertan Kucuksayan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
apoptosis, gambogic acid, neuroserpin, oxidative stress, triple-negative breast cancer