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 RheumpalmatumL. are able to block epidermal growth factor (EGF)‑ and tissue plasminogen activator‑induced JB6 C141cell transformation. The aloe emodin treatment was applied to the JB6C141cell neoplastic model. The toxicity of aloe emodin was determined. The present study detected the expression level of AKT serine/threonine kinase1 (AKT), lysine‑tRNA ligase MSK1(MSK1) and cyclinD1 using western blotting. The cell proliferation and cell cycle distribution were also monitored. And when 95‑maximal effective dose ranged between 1 and15µM, 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 kinase1 and glycogen synthase kinase3β (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/Scell cycle transition. Cyclin D1 transcriptional activity was reduced to 25%, 24h following aloe emodin treatment. The protein expression of cyclinD1 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.