Jolkinolide B induces apoptosis in MCF-7 cells through inhibition of the PI3K/Akt/mTOR signaling pathway
Authors: Zhi-Wei Chen
Feng-Xia Du
Ji-Cheng Liu
Hui-Yu Xu
Jin-Cai Hou
Journal: Oncology Reports (2013)
Discipline: CLINICAL MEDICINE
Keywords: molecular mechanisms; jolkinolide B; PI3K/Akt/mTOR signaling pathway; proliferation; apoptosis
Affiliations: Department of Immunology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, PR China.

Abstract:  The aim of this study was to explore the molecular mechanisms of jolkinolide B (JB), which is extracted from the root of Euphorbia fischeriana Steud. In this study, we found that JB, a diterpenoid from the traditional Chinese medicinal herb, strongly inhibited the PI3K/Akt/mTOR signaling pathway. Furthermore, we evaluated the effects of JB on the proliferation and apoptosis of MCF-7 human breast cancer cells. Our results showed significant induction of apoptosis in MCF-7 cells incubated with JB. The viability of the MCF-7 cells was assessed by MTT assay. Flow cytometry was used to detect apoptosis and cell cycle analysis. Transmission electron microscopy (TEM) analysis was used to observe cell morphology. MCF-7 cells were subcutaneously inoculated into nude mice to study the in vivo antitumor effects of JB. The growth of MCF-7 cells was inhibited and arrested in the S phase by JB. The data showed significantly decreased tumor volume and weight in nude mice inoculated with MCF-7 cells. In addition, treatment with JB was able to induce downregulation of cyclinD1, cyclinE, mTOR, p-PI3K and p-Akt, and upregulation of PTEN and p-eIF4E. Collectively, JB-induced apoptosis of MCF-7 cells occurs through the PI3K/Akt/mTOR signaling pathway. Furthermore, the PI3K/Akt signaling cascade plays a role in the induction of apoptosis in JB-treated cells. These observations suggest that JB may have therapeutic applications in the treatment of cancer. 

Retracted: No

PubPeer comments:
 *[right]* Figure 6 from [Xu et al (2013)] .  Effect of JB on the PI3K Akt mTOR signal pathway in tumor tissues. Proteins were extracted, then cyclinD1, cyclinE, p-PI3K, p-Akt, PTEN, mTOR and p-eIF4E expressions were determined by western blot analysis. *[left]* Figure 7 from [Yang et al (2019] .  Isoacteoside inhibited the AKT PI3K mTOR pathway as shown by western blot analysis. ![file] , 
 *[right]* Figure 6 from [Xu et al (2013)] .  Effect of JB on the PI3K Akt mTOR signal pathway in tumor tissues. Proteins were extracted, then cyclinD1, cyclinE, p-PI3K, p-Akt, PTEN, mTOR and p-eIF4E expressions were determined by western blot analysis. *[left]* Figure 8 from [Li et al (2019)] .  Effect of Ginsenoside (Rg1) on the mTOR PI3K AKT pathway in SUNE1 cells at indicated concentrations as depicted by western blot analysis . ![file] , 
 #1 Improved comparison. ![file] For further comparison: Figure 9 from [Zhao et al (2016)] .  Effect of amarogentin on the m-TOR, cyclin D1, cyclin E, PI3K Akt pathways in human gastric (SNU16) cancer cells. The expressions of these proteins were evaluated by Western blot analysis . ![file] , 
 #3 Another sighting! Fig 5(c) from [Jin et al (2016)] .  c Protein levels of PTEN-regulated genes following miRNA-141-3p inhibitor transfection also subsequently changed. ![file] ,