Toosendanin induces apoptosis of MKN‑45 human gastric cancer cells partly through miR‑23a‑3p‑mediated downregulation of BCL2.

Abstract

Toosendanin (TSN) is a tetracyclic triterpenoid extracted from Melia toosendan Sieb, et Zucc, which primarily grows in specific areas of China. Although toosendanin (TSN) exerts antitumoral effects on various human cancer cells, its influence on gastric cancer (GC) is remains to be elucidated. MicroRNAs (miRNAs/miRs) serve crucial roles in apoptosis and proliferation of cancer cells. miR‑23a‑3p has been shown to be associated with human GC; however, the specific function of miR‑23a‑3p in GC remains unclear. Therefore, the present study aimed to elucidate the role of miR‑23a‑3p in the regulation of GC cell proliferation and apoptosis induced in vitro by TSN treatment. Subsequently, apoptosis‑related genes expression levels were quantified by reverse transcription‑quantitative PCR and western blot analysis, respectively, and the target relationship between miR‑23a‑3p and BCL2 was determined by luciferase reporter gene analysis. Additionally, cell proliferation and apoptosis experiments were carried out. The results indicated that TSN inhibited proliferation and induced apoptosis in MKN‑45 cells. Moreover, it upregulated the expression of miR‑23a‑3p. B‑cell lymphoma‑2 (BCL2) was identified as a potential target gene of miR‑23a‑3p, which was demonstrated to bind to the 3'‑untranslated region of BCL2 mRNA, as detected by the luciferase reporter assay. Further studies revealed that BCL2 expression was downregulated following overexpression of miR‑23a‑3p. In addition, the overexpression of the miR‑23a‑3p inhibited proliferation, induced G1 arrest and increased apoptosis in MKN‑45 cells. The results of the present study demonstrated that miR‑23a‑3p inhibited proliferation and induced apoptosis of GC cells, which may be attributable to its direct targeting of BCL2. These results may provide a novel insight into the apoptosis of GC cells, and may lead to investigations into the mechanisms of the effects of TSN.

• Authors: Shuli Shao, Shanshan Li, Chang Liu, Weiwei Zhang, Zhenzhu Zhang, Shaowei Zhu, Yunjianan Feng, Yang Pan
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 22 Issue 3 Pg. 1793-1802 (09 2020) ISSN: 1791-3004 [Electronic] Greece
• PMID: 32582989 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• BCL2 protein, human
• Drugs, Chinese Herbal
• MIRN23a microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins c-bcl-2
• toosendanin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Cycle Checkpoints
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Down-Regulation
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MicroRNAs (genetics)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Stomach Neoplasms (drug therapy, genetics)