2. Academic Validation
  3. α-Cyperone inhibits the proliferation of human cervical cancer HeLa cells via ROS-mediated PI3K/Akt/mTOR signaling pathway

α-Cyperone inhibits the proliferation of human cervical cancer HeLa cells via ROS-mediated PI3K/Akt/mTOR signaling pathway

  • Eur J Pharmacol. 2020 Sep 15;883:173355. doi: 10.1016/j.ejphar.2020.173355.
Xiao-Dong Pei 1,  Hong-Liang Yao 2,  Li-Qun Shen 3,  Yang Yang 4,  Lan Lu 5,  Jun-Song Xiao 6,  Xin-Yu Wang 7,  Zhi-Long He 7,  Li-He Jiang 8
Affiliations

Affiliations

  • 1 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563100, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China; College of Light Industry and Food Engineering, Guangxi University, Nanning, Guangxi, 530004, PR China.
  • 2 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Drug Synthesis and Evaluation Center, Guangdong Institute of Applied Biological Resources, Guangdong, PR China.
  • 3 Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi University for Nationalities, Nanning, 530006, PR China.
  • 4 Department of Pharmacology, Guilin Medical University, Guilin, Guangxi, 541000, PR China.
  • 5 Sichuan Industrial Institute of Antibiotics, Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Chengdu University, 610106, Chengdu, PR China.
  • 6 Beijing Higher Institution Engineering Research Center of Food Additives and Ingredients, Beijing Technology and Business University-BTBU, Beijing, 100048, PR China.
  • 7 College of Light Industry and Food Engineering, Guangxi University, Nanning, Guangxi, 530004, PR China.
  • 8 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563100, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China; College of Light Industry and Food Engineering, Guangxi University, Nanning, Guangxi, 530004, PR China; Medical College, Guangxi University, Nanning, 530004, PR China; School of Basic Medical Science, YouJiang Medical University for Nationaties, No. 98 Chengxiang Road, Baise, Guangxi, 533000, PR China. Electronic address: jianglihe@gxu.edu.cn.
PMID: 32687921 DOI: 10.1016/j.ejphar.2020.173355
Abstract

Cervical Cancer is the fourth leading killer of female Cancer patients worldwide. Each year more than half a million women are diagnosed with cervical Cancer and the disease results in over 300, 000 deaths. α-Cyperone is known as the principal active ingredient in the Cyperus rotundus (Family: Cyperaceae). However, the effects of α-Cyperone on cancers, especially on cervical Cancer, are yet to be explored. In the present study, the underlying mechanism of the anti-tumor activity of α-Cyperone against HeLa cells was investigated. The results showed that α-Cyperone inhibited proliferation and induced Apoptosis in HeLa cells. Mechanistically, α-Cyperone promoted HeLa cells Apoptosis via a mitochondrial apoptotic pathway, which was proved by increased level of intracellular Reactive Oxygen Species (ROS) and upregulated expression of cytochrome c, cleaved Caspase-3, PARP, and Bax. Further RNA-sequencing revealed α-Cyperone inhibited the activation of PI3K/Akt/mTOR signaling pathway in HeLa cells, which confirmed by PI3K Inhibitor and agonist. The PI3K Inhibitor (LY294002) synergized with α-Cyperone in arresting the growth of HeLa cells, whereas the PI3K agonist (IGF-1) abrogated such an effect. Interestingly, the expression of PD-L1 was attenuated by both α-Cyperone and LY294002, while the supplement of IGF-1 rescued the low expression of PD-L1. In conclusion, our results reveal that the inhibitory effect of α-Cyperone on HeLa cell growth is triggered via the ROS-mediated PI3K/Akt/mTOR signaling pathway and closely related to a decline in the PD-L1 expression.

Keywords

Apoptosis; HeLa cells; PD-L1; PI3K/Akt/mTOR signaling pathway; α-Cyperone.

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