Betulinic acid isolated from Betula platyphylla   induces apoptosis and reduces the mTOR/PI3K/AKT   signaling pathway in endometrial cancer cells

Ceren Oy; Mücahit Secme; Duygu Gok Yurtseven; Sema Serter Koçoğlu; Gözde Korkusuz Akçal

Publication:
Betulinic acid isolated from Betula platyphylla induces apoptosis and reduces the mTOR/PI3K/AKT signaling pathway in endometrial cancer cells

dc.contributor.author	Ceren Oy
dc.contributor.author	Mücahit Secme
dc.contributor.author	Duygu Gok Yurtseven
dc.contributor.author	Sema Serter Koçoğlu
dc.contributor.author	Gözde Korkusuz Akçal
dc.contributor.department	Biología Celular e Histología
dc.date.accessioned	2026-02-16T10:14:44Z
dc.date.available	2026-02-16T10:14:44Z
dc.date.issued	2026
dc.description.abstract	Endometrial cancer is one of the most common gynecological cancers worldwide, and an average of 42,000 women die each year. Chemotherapy, radiotherapy, and surgery are among the treatments available for endometrial cancer. Currently, drugs used for chemotherapy have had limited success in increasing the cure rate. Betulinic acid, a lupane-type triterpene widely found in the plant kingdom, has attracted attention for cancer treatment in recent years due to its ability to inhibit tumor growth and induce cell apoptosis. The aim of this study is to investigate the mTOR pathway-mediated anticancer effects of betulinic acid in human endometrial cancer cells. The effect of betulinic acid on Ishikawa cell viability was determined by the CCK-8 method. Its effect on the expression of genes involved in apoptosis and the mTOR pathway was assessed by real-time PCR. The effect on protein expression in the mTOR pathway was evaluated with immunohistochemistry and western blot, and the effects on apoptosis via Annexin V. Betulinic acid reduced Ishikawa endometrial cancer cell proliferation. Betulinic acid administration caused a significant decrease in Bcl2 (p=0.008) expression and increased caspase-8 (p=0.001) expression in Ishikawa cells. The results of Annexin V supported the idea that betulinic acid administration triggered apoptosis in Ishikawa cells. The mean rate of apoptotic cells in the betulinic acid group was 22±3.23%, while it was 2.31±0.2% in the control group (p=0.02). Betulinic acid caused a significant decrease in the expression of AKT1 (p=0.0001) and a significant increase in the expression of RAPTOR (p=0.00002). Betulinic acid administration also significantly percentage of p-PI3K, p-AKT, and p-mTOR-positive cells in Ishikawa cells was 89.39±5.19%, 74.84%±5.07, and 82.02%±6.14, respectively, in the control group. In the betulinic acid group, these values were 49.12± 19.12% (p=0.002), 44.46±7.39% (p<0.001), and 53.70±8.94% (p<0.001), respectively. This study showed that betulinic acid decreased Ishikawa cell proliferation, triggered apoptosis, and decreased mTOR signaling; thus, betulinic acid may be a potential anticancer agent for the treatment of endometrial cancer. decreased protein expression in the mTOR pathway. The
dc.format	application/pdf
dc.format.extent	9
dc.identifier.doi	https://doi.org/10.14670/HH-18-960
dc.identifier.eissn	1699-5848
dc.identifier.issn	0213-3911
dc.identifier.uri	http://hdl.handle.net/10201/205581
dc.language	eng
dc.relation	Universidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.relation	Sin financiación externa a la Universidad
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 International	*
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Endometrial cancer
dc.subject	Ishikawa cells, Apoptosis
dc.subject	mTOR
dc.subject	Betulinic acid
dc.subject.ods	No relacionado con ningún objetivo de desarrollo sostenible
dc.title	Betulinic acid isolated from Betula platyphylla induces apoptosis and reduces the mTOR/PI3K/AKT signaling pathway in endometrial cancer cells
dc.type	info:eu-repo/semantics/article
dspace.entity.type	Publication