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α-Tomatine, a novel early-stage autophagy inhibitor, inhibits autophagy to enhance apoptosis via Beclin-1 in Skov3 cells.

Authors
  • Wu, Hailun1
  • Li, Weibin2
  • Wang, Tingting3
  • Rong, Yan1
  • He, Ziying1
  • Huang, Siting1
  • Zhang, Lifan3
  • Wu, Zuoxing3
  • Liu, Chanzhen4
  • 1 Department of Gynecological Oncology, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, 530000, China. , (China)
  • 2 Xiang'An Hospital of Xiamen University, Xiamen, 361000, China. , (China)
  • 3 Department of Nuclear Medicine, Zhongshan Hospital, Xiamen University, Xiamen, 361000, China. , (China)
  • 4 Department of Gynecological Oncology, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, 530000, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Fitoterapia
Publication Date
Jul 01, 2021
Volume
152
Pages
104911–104911
Identifiers
DOI: 10.1016/j.fitote.2021.104911
PMID: 33901572
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Targeting the autophagy process is considered to be a promising new strategy for drug treatment of ovarian cancer. α-Tomatine, a steroidal alkaloid extracted, is mainly isolated from leaves, roots and immature green tomatoes. α-Tomatine has biological activities such as anticancer, antioxidative and anti-inflammatory. The study aimed to explore the effects of α-tomatine on proliferation, apoptosis and autophagy and the underlying mechanisms in ovarian cancer Skov3 cells. After treatment with different concentrations of α-tomatine (0, 0.75, 1 and 1.5 μM) in Skov3 cells for 24 h, proliferation was determined by the CCK-8 assay, and apoptosis was detected by flow cytometric analysis. Autophagy in cells was determined by the number of fluorescent spots using confocal fluorescence microscopy after mRFP-GFP-LC3 transfection. The relationship between autophagy and apoptosis was proved by Beclin-1 overexpression. The protein expression levels were tested by western blotting. The results demonstrated that α-tomatine effectively repressed proliferation, exerted a proapoptotic effect and inhibited early-stage autophagy in Skov3 cells in a dose- and time-dependent manner. Additionally, Beclin-1 overexpression significantly suppressed α-tomatine-treated apoptosis in Skov3 cells, indicating that α-tomatine inhibits autophagy to induce apoptosis. We also found α-tomatine inhibited the protein expression levels of PI3K/Akt/mTOR signaling pathway. However, the autophagy inhibition of α-tomatine could be reversed obviously by Beclin-1 overexpression. Taken together, α-tomatine inhibited autophagy through Beclin-1. Our study suggests that α-tomatine, as a novel early-stage autophagy inhibitor, might be a potential drug for further treatment of ovarian cancer by inhibiting proliferation and promoting apoptosis. Copyright © 2021 Elsevier B.V. All rights reserved.

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