|Table of Contents|

The mechanistic analysis of Siha apoptosis and ferroptosis caused in cervical cancer cells by Pseudolaric acid B up-regulation of HMOX1

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 18
Page:
3413-3419
Research Field:
Publishing date:

Info

Title:
The mechanistic analysis of Siha apoptosis and ferroptosis caused in cervical cancer cells by Pseudolaric acid B up-regulation of HMOX1
Author(s):
DONG Jingjing1SHI Shaoqing2LI Yuqiong1NIU Lulu1SUN Ruifen1
1.Yunnan University of Traditional Chinese Medicine,Yunnan Kunming 650500,China;2.The First Affiliated Hospital of Kunming Medical University,Yunnan Kunming 650032,China.
Keywords:
Pseudolaric acid B (PAB)ferroptosiscervical cancer
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2024.18.003
Abstract:
Objective:To explore the mechanism of apoptosis and ferroptosis mediated by PAB(Pseudolaric acid B,PAB)in cervical cancer Siha cells.Methods:The cytotoxicity of PAB on Siha was determined using the CCK8 test.Annexin V-FITC and PI double fluorescence labeling were used to detect apoptosis.Fluorescence microscopy was used to assess nuclear morphology and cell death after labeling with PI and Hochest.The cell cycle and intracellular reactive oxygen species (ROS) levels were determined using flow cytometry.Inverted fluorescence microscopy with BODIPYTM 581/591 C11 labeling to detect intracellular lipid peroxidation products.Fluorescence microscopy was used to monitor intracellular mitochondrial membrane potential changes using JC-1 labeling.Western blot analysis revealed the expression of ferroptosis-associated proteins GPX4,SLC7A11,Ferritin,and HMOX1,as well as apoptosis-related proteins PARP,c-IAP1,c-IAP2,XIAP,and Survivin.The mRNA expression levels of ferroptosis-related genes were determined using RT-PCR.Results:PAB dramatically reduced the proliferation of cervical cancer Siha cells,induced apoptosis,and stopped the cell cycle.Second,PAB increased intracellular ROS levels,lipid peroxide buildup,and mitochondrial membrane potential increases.Meanwhile,it increased the expression of HMOX1 protein and mRNA,decreased the expression of GPX4,SLC7A11 protein and mRNA,and decreased the expression of Ferritin,c-IAP1,c-IAP2,XIAP,and Survivin.Conclusion:PAB dramatically increased cell death in cervical cancer Siha cells,and the mechanism of action may be connected to HMOX1 overexpression to trigger apoptosis and ferroptosis.

References:

[1]SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2]MANRRIQUEZ EN,ZAKHOUR M,SALANI R.Precision medicine for cervical cancer[J].Curr Opin Obstet Gynecol,2022,34(1):1-5.
[3]罗健玮,黄泓轲,胡艳丽.LncRNA GATA3-AS1通过调控miR-362-3p/FABP5轴抑制宫颈癌细胞增殖、迁移及侵袭[J].现代肿瘤医学,2024,32(06):1009-1016. LUO JW,HUANG HK,HU YL.LncRNA GATA3-AS1 inhibits the proliferation,migration and invasion of cervical cancer cells by regulating the miR-362-3p/FABP5 axis[J].Modern Oncology,2024,32(06):1009-1016.
[4]ZHANG C,LIU X,JIN S,et al.Ferroptosis in cancer therapy:a novel approach to reversing drug resistance[J].Mol Cancer,2022,21(1):47.
[5]MOU Y,WANG J,WU J,et al.Ferroptosis,a new form of cell death:opportunities and challenges in cancer[J].J Hematol Oncol,2019,12(1):34.
[6]LEI G,ZHUANG L,GAN B.Targeting ferroptosis as a vulnerability in cancer[J].Nat Rev Cancer,2022,22(7):381-396.
[7]LIU C,WANG F,WANG B,et al.Pseudolaric acid B induces apoptosis in human rhabdomyosarcoma RD cells[J].Oncol Lett,2020,20(6):358.
[8]YIN M,LI N,ZHANG L,et al.Pseudolaric acid B ameliorates fungal keratitis progression by suppressing inflammation and reducing fungal load[J].ACS Infect Dis,2023,9(6):1196-1205.
[9]刘景,方崇锴,王陵军,等.土荆皮乙酸诱导鼻咽癌细胞铁死亡的作用及机制[J].中华中医药学刊,2023,41(11):82-85,272. LIU J,FANG CK,WANG LJ,et al.Role and mechanism of ferroptosis in nasopharyngeal carcinoma cells induced by pseudolaric acid B[J].Chinese Archives of Traditional Chinese Medicine,2023,41(11):82-85,272.
[10]MIAO Y,YIN Q,PING L,et al.Pseudolaric acid B triggers ferritinophagy and ferroptosis via upregulating NCOA4 in lung adenocarcinoma cells[J].J Cancer Res Ther,2023,19(6):1646-1653.
[11]李斌,段淑莉,王思成,等.金钱松化学成分及药理活性研究进展 [J].中草药,2021,52(19):6096-6061.LI B,DUAN SL,WANG SC,et al.Research progress on chemical constituents and pharmacological activities of Pseudolarix amabilis[J].Chinese Traditional and Herbal Drugs,2021,52(19):6096-6061.
[12]LIU Z,WANG N,MENG Z,et al.Pseudolaric acid B triggers cell apoptosis by activating AMPK/JNK/DRP1/mitochondrial fission pathway in hepatocellular carcinoma[J].Toxicology,2023,493:153556.
[13]LI X,ZHAO X,SONG W,et al.Pseudolaric acid B inhibits proliferation,invasion and epithelial-to-mesenchymal transition in human pancreatic cancer cell[J].Yonsei Med J,2018,59(1):20-27.
[14]WANG Z,DING Y,WANG X,et al.Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT[J].Cancer Lett,2018,428:21-33.
[15]YU F,LI K,CHEN S,et al.Pseudolaric acid B circumvents multidrug resistance phenotype in human gastric cancer SGC7901/ADR cells by downregulating Cox-2 and P-gp expression[J].Cell Biochem Biophys,2015 J,71(1):119-126.
[16]CARNEIRO BA,EL-DEIRY WS.Targeting apoptosis in cancer therapy[J].Nat Rev Clin Oncol,2020,17(7):395-417.
[17]TANG D,CHEN X,KANG R,et al.Ferroptosis:molecular mechanisms and health implications[J].Cell Res,2021,31(2):107-125.
[18]CHEN T,LIANG L,WANG Y,et al.Ferroptosis and cuproptposis in kidney diseases:dysfunction of cell metabolism[J].Apoptosis,2024,29(3-4):289-302.
[19]ZHANG HL,HU BX,LI ZL,et al.PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis[J].Nat Cell Biol,2022,24(1):88-98.
[20]WANG Z,LI W,WANG X,et al.Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells[J].Chin Med J (Engl),2023,136(18):2210-2220.

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云南省科技厅科技计划项目[编号:202201AT070043,2019FF002(-011)]
Last Update: 1900-01-01