NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2022, Vol. 34 ›› Issue (3): 359-367.doi: 10.16333/j.1001-6880.2022.3.001

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Exploring the effect of licochalcone A from Xinjiang Glycyrrhiza inflata Bat.on proliferation and apoptosis of cervical cancer cells and its molecular mechanism based on CADD

AIZITIAILI·Aihaiti,YANG Zheng,MOURBOUL·Ablise*,MIHRIGUL·Mamtimin,SAILIKEALA·Alihan,YUSUPUWAJIMU·Alimujiang#br# #br#
  

  1. College of Pharmacy,Xinjiang Medical University,Urumqi 830011,China
  • Online:2022-03-28 Published:2022-03-28

Abstract:

In this study,licochalcone A (LicoA) was used as the substance basis to study its proliferation inhibitory activity,apoptotic and cell cycle arresting effect on cervical cancer cells,and its molecular mechanism was initially investigated.LicoA was purified from Xinjiang Glycyrrhiza inflata Bat.,and its chemical structure was identified by 1H NMR,13C NMR and HR-EI-MS methods.The inhibition rate of LicoA on human cervical cancer cells (SiHa and HeLa) at different concentrations was detected by MTT assay and IC50 value was calculated.SiHa cells were selected as research object,flow cytometry was used to detect the apoptosis rate of cells by Annexinv-FITC/PI double staining,and the effect on cell cycle was determined.The CADD method was used to predict the possible target of LicoA.The mRNA expression levels of marker (Bcl-2,ALDH1A1,OCT-4,UHRF1,BIRC7,BIRC5) and cyclin-dependent kinase 4 (cyclin-dependent kinase 4,CDK4) were detected by fluorescence qRT-PCR method.The results showed that LicoA could significantly inhibit the proliferation of the two cervical cancer cells in a time-dependent and concentration-dependent manner.With the increase of LicoA concentration,the cell proliferation rate slowed,and the cells showed a shrunken form.LicoA induced apoptosis significantly,and the apoptosis rate of SiHa cells reached 52.0% at 30 μg/mL.LicoA may block the proliferation cycle of SiHa cells in S and G2/M phase.Molecular docking results showed that LicoA had a good binding ability to CDK4 protein,and predicted that LicoA might have a strong inhibitory activity.LicoA significantly down-regulated the expression of stem cell markers Bcl-2,ALDH1A1,OCT-4,UHRF1,BIRC7 and BIRC5,and inhibited the mRNA expression of CDK4.The mechanism that LicoA can inhibit the proliferation of SiHa may be by arresting the proliferation cycle of SiHa in S phase and G2/M phase,inducing cell apoptosis,and inhibiting cell differentiation.

Key words: licochalcone A, cervical cancer cells, proliferation inhibitory activity, flow cytometry, CADD, tumor stem cell markers

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