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Original Research

Open Access

Jolkinolide B induces reactive oxygen species accumulation and endoplasmic reticulum stress and inhibits MAPK and AKT signaling activation in renal cancer cells

  • Xuan Wu1,†
  • Sijing Pan2,†
  • Xiujuan Li1
  • Jing Liu1
  • Zhigang Wang1
  • Yinghong Lei1
  • Qunchao Mei1,*,

1Department of Geriatrics, Wuhan NO.1 Hospital, 430000 Wuhan, Hubei, China

2Department of Neurology, Wuhan NO.1 Hospital, 430000 Wuhan, Hubei, China

DOI: 10.22514/jomh.2024.078 Vol.20,Issue 5,May 2024 pp.119-125

Submitted: 15 March 2024 Accepted: 25 April 2024

Published: 30 May 2024

*Corresponding Author(s): Qunchao Mei E-mail: meiqunchao3111001@163.com

† These authors contributed equally.

Abstract

To investigate the impact of Jolkinolide B (JB) on renal cell carcinoma (RCC), we treated RCC cell lines with various concentrations of JB (0, 5, 25, 50 and 100 µM) for 24 hours and assessed cell viability using the cell counting kit-8 (CCK-8) analysis. Then, we examined JB’s effects on proliferation, migration, apoptosis, reactive oxygen species (ROS) accumulation, and endoplasmic reticulum (ER) stress through 5-ethynyl-2′-deoxyuridine (EdU) incorporation, transwell migration assays, flow cytometry, ROS level determination, and western blot assays. Furthermore, we investigated the potential mechanism using western blot. Our results showed that JB dose-dependently reduced cell viability in both 786-O and Caki1 cells. Additionally, JB at concentrations of 5, 25 and 50 µM decreased the number of EdU-positive and migrating cells in both cell lines. Additionally, these concentrations of JB increased apoptosis rates, relative protein expressions of cleaved caspase-3 and cleaved caspase-9, ROS levels, and relative protein expressions of C/EBP-homologous protein (CHOP) and activated transcription factor 4 (ATF4) in both 786-O and Caki1 cells. Mechanistically, treatment with all three concentrations of JB significantly downregulated phosphorylated p38 (p-p38)/p38, phosphorylated protein kinase B (p-AKT)/AKT and phosphorylated phosphatidylinositol-3-kinase (p-PI3K)/PI3K in a dose-dependent manner. In summary, JB inhibited proliferation and migration while promoting apoptosis, ROS accumulation, and ER stress in RCC cells, potentially through the inactivation of mitogen-activated protein kinase (MAPK) and AKT signaling pathways.


Keywords

Renal cancer; Jolkinolide B; ROS; Endoplasmic reticulum stress; MAPK; AKT


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Xuan Wu,Sijing Pan,Xiujuan Li,Jing Liu,Zhigang Wang,Yinghong Lei,Qunchao Mei. Jolkinolide B induces reactive oxygen species accumulation and endoplasmic reticulum stress and inhibits MAPK and AKT signaling activation in renal cancer cells. Journal of Men's Health. 2024. 20(5);119-125.

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