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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.

References

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annual Review of Pathology: Mechanisms of Disease. 2021; 16: 223–249.

[3] Zhang YY, Yan Y, Zhang J, Xia CY, Lian WW, Wang WP, et al. Jolkinolide B: a comprehensive review of its physicochemical properties, analytical methods, synthesis and pharmacological activity. Phytochemistry. 2022; 204: 113448.

[4] Zhang H, Qian J, Jin M, Fan L, Fan S, Pan H, et al. Jolkinolide B induces cell cycle arrest and apoptosis in MKN45 gastric cancer cells and inhibits xenograft tumor growth in vivo. Bioscience Reports. 2022; 42: BSR20220341.

[5] Sang J, Li W, Diao H, Fan R, Huang J, Gan L, et al. Jolkinolide B targets thioredoxin and glutathione systems to induce ROS-mediated paraptosis and apoptosis in bladder cancer cells. Cancer Letters. 2021; 509: 13–25.

[6] Wang Y, Shen S, Liu L, Zhang X, Liu D, Liu N, et al. Jolkinolide B inhibits proliferation or migration and promotes apoptosis of MCF-7 or BT-474 breast cancer cells by downregulating the PI3K-Akt pathway. Journal of Ethnopharmacology. 2022; 282: 114581.

[7] Zhang J, Wang Y, Zhou Y, He Q. Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+—mitochondria dependent pathway. Oncotarget. 2017; 8: 91223–91237.

[8] Gao C, Yan X, Wang B, Yu L, Han J, Li D, et al. Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis. Scientific Reports. 2016; 6: 36114.

[9] Bi M, Sun J, Wang F, Li S. Knockdown of RBBP6 enhances radiosensitivity of gastric cancer cells through p53 pathway. Molecular & Cellular Toxicology. 2022; 18: 599–604.

[10] Liou G, Storz P. Reactive oxygen species in cancer. Free Radical Research. 2010; 44: 479–496.

[11] Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews Drug Discovery. 2009; 8: 579–591.

[12] Goodman M, Bostick RM, Kucuk O, Jones DP. Clinical trials of antioxidants as cancer prevention agents: past, present, and future. Free Radical Biology and Medicine. 2011; 51: 1068–1084.

[13] Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiological Reviews. 2007; 87: 99–163.

[14] Martinon F. Targeting endoplasmic reticulum signaling pathways in cancer. Acta Oncologica. 2012; 51: 822–830.

[15] Sang J, Gan L, Zou M, Lin Z, Fan R, Huang J, et al. Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy. Cancer Letters. 2022; 526: 352–362.

[16] Wei C, Zhou W. Hypaphorine ameliorates lipid accumulation and inflammation in a cellular model of non-alcoholic fatty liver by regulating p38/JNK and NF-κB signaling pathways. Tropical Journal of Pharmaceutical Research. 2022; 21: 2569–2574.

[17] Zhan Y, Liu J, Qu X, Hou K, Wang K, Liu Y, et al. Β-elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathways. Asian Pacific Journal of Cancer Prevention. 2012; 13: 2739–2744.

[18] Zhong W, Wang X, Pan B, Li F, Kuang L, Su Z. Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways. Oncology Letters. 2016; 12: 2894–2899.

[19] Liu H, Li X, Duan Y, Xie J, Piao X. Mechanism of gypenosides of Gynostemma pentaphyllum inducing apoptosis of renal cell carcinoma by PI3K/AKT/mTOR pathway. Journal of Ethnopharmacology. 2021; 271: 113907.


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