Publication: Betulinic acid isolated from Betula platyphylla induces apoptosis and reduces the mTOR/PI3K/AKT signaling pathway in endometrial cancer cells
Authors
Ceren Oy ; Mücahit Secme ; Duygu Gok Yurtseven ; Sema Serter Koçoğlu ; Gözde Korkusuz Akçal
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Publisher
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DOI
https://doi.org/10.14670/HH-18-960
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info:eu-repo/semantics/article
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
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