Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential

Zhang,Qianying; Li,Xing; He,Caiyi; Zhou,Rongmiao; Wang,Jing; Liu,Liang

doi:10.3892/ol.2024.14447

Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential

Authors:
- Qianying Zhang
- Xing Li
- Caiyi He
- Rongmiao Zhou
- Jing Wang
- Liang Liu
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Affiliations: Department of Gynaecological Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Flow Cytometry, Tumour Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Molecular Biology, Tumour Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: May 14, 2024 https://doi.org/10.3892/ol.2024.14447
Article Number: 315
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth‑inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit‑8 assay after treatment with ART for 24 h, after which the half‑maximal inhibitory concentration (IC₅₀) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca²⁺) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl‑xl, (myeloid cell leukaemia 1) Mcl‑1, Bcl2‑like protein 11 (BIM), (Bcl2‑related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription‑quantitative PCR. ART inhibited the growth of SiHa cells in a dose‑dependent manner. The IC₅₀ of ART in SiHa cells was 26.32 µg/ml. According to the IC₅₀ value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca²⁺ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl‑xl and Mcl‑1 in a dose‑ and time‑dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca²⁺ and the reduction of the mitochondrial membrane potential.

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