Aloe emodin suppresses EGF‑induced neoplastic cell transformation by inhibiting the ERK/MSK1 and AKT/GSK3β signaling pathways.

Abstract

Natural compounds which can block cell transformation due to potential for chemoprevention have received increased attention. The present study aimed to investigate whether aloe emodin, which is present in aloe latex or the roots of the Rheum palmatum L. are able to block epidermal growth factor (EGF)‑ and tissue plasminogen activator‑induced JB6 C141 cell transformation. The aloe emodin treatment was applied to the JB6 C141 cell neoplastic model. The toxicity of aloe emodin was determined. The present study detected the expression level of AKT serine/threonine kinase 1 (AKT), lysine‑tRNA ligase MSK1 (MSK1) and cyclin D1 using western blotting. The cell proliferation and cell cycle distribution were also monitored. And when 95‑maximal effective dose ranged between 1 and 15 µM, the cell death was evident. Aloe emodin‑treated cells had an impaired anchorage‑independent growth capability, leading to a dose‑dependent reduction of colony formation. Western blotting revealed that aloe emodin had a significant effect on phosphorylation of pyruvate dehydrogenase kinase 1 and glycogen synthase kinase 3β (GSK3β) and AKT was inhibited. The present study determined that the proliferation of JB6 C141 cells was reduced in a dose‑dependent manner and the effect may be associated with its inhibition of the G1/S cell cycle transition. Cyclin D1 transcriptional activity was reduced to 25%, 24 h following aloe emodin treatment. The protein expression of cyclin D1 was inhibited. The findings of the present study indicated that aloe emodin may be able to suppress neoplastic cell transformation by inhibiting the extracellular‑signal regulated kinase/MSK1 and AKT/GSK3β signaling pathways. It may be a potential natural compound for chemoprevention.

• Authors: Juan Zhang, Lihua Guo, Quanwu Zhang, Kangdong Liu, Ziming Dong
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 18 Issue 6 Pg. 5215-5220 (Dec 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 30272294 (Publication Type: Journal Article)

Chemical References

• Anthraquinones
• Antineoplastic Agents
• Cyclin D1
• Epidermal Growth Factor
• aloe emodin
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 90-kDa
• mitogen and stress-activated protein kinase 1
• Extracellular Signal-Regulated MAP Kinases

Topics

• Anthraquinones (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Transformation, Neoplastic (drug effects, genetics, metabolism)
• Cyclin D1 (genetics, metabolism)
• Dose-Response Relationship, Drug
• Epidermal Growth Factor (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation (drug effects)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ribosomal Protein S6 Kinases, 90-kDa (metabolism)
• Signal Transduction (drug effects)