Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells

XIA Yuan; JIANG Qingling; WANG Xiaoting; LI Minjing; ZHENG Qiusheng; LI Defang

doi:10.11665/j.issn.1000-5048.2023033004

Journal of China Pharmaceutical University > 2023 > 54(6): 757-768. > DOI: 10.11665/j.issn.1000-5048.2023033004

XIA Yuan, JIANG Qingling, WANG Xiaoting, LI Minjing, ZHENG Qiusheng, LI Defang. Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells[J]. Journal of China Pharmaceutical University, 2023, 54(6): 757-768. DOI: 10.11665/j.issn.1000-5048.2023033004

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Norcantharidin induces apoptosis through autophagosome accumulation in breast cancer MDA-MB-231 cells

1.
Key Laboratory of Xinjiang Phytomedicine Resource and Utilization (Ministry of Education), School of Pharmacy, Shihezi University, Shihezi 832061
2.
Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003
3.
Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81872162)

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Received Date: March 29, 2023
Revised Date: September 25, 2023

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Abstract

Abstract

The aim of this study was to investigate the effect of norcantharidin (NCTD) on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231.Western blot was used to detect the effect of NCTD on the expression levels of apoptosis-related proteins Bax/Bcl-2, cleaved-PARP/PARP/PARP, cleved-caspase-9, cleaved-caspase-3 and MCL-1 in MDA-MB-231 cells.Also, the expression levels of autophagy-related proteins LC3-II/LC3-I, Parkin and PINK1 in MDA-MB-231 cells were measured by Western blot.Flow cytometry was used to measure the effect of NCTD on the changes of mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS).The effect of NCTD on autophagy flow in cells expressing mCherry-EGFP-LC3 was detected by a confocal microscope.Moreover, the effects of NCTD combined with chloroquine (CQ) or 3-methyladenine (3-MA) on the apoptosis of MDA-MB-231 cells were detected by flow cytometry.The results showed that NCTD significantly increased the expression levels of Bax/Bcl-2, cleaved-PARP/PARP, cleaved-caspase-9, cleasved-caspase-3 and LC3-II/LC3-I proteins, and promoted the mitochondrial translocation of Parkin, and blocked the autophagic flow in MDA-MB-231 cells. Moreover, NCTD combined with CQ accelerated apoptosis, while NCTD combined with 3-MA decreased apoptosis.These results suggest that NCTD can induce autophagy accumulation and lead to apoptosis of MDA-MB-231 cells.
- breast cancer,
- MDA-MB-231 cells,
- norcantharidin,
- apoptosis,
- autophagy

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References (35)

References

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