Sanguinarine inhibits the proliferation of BGC-823 gastric cancer cells via regulating miR-96-5p/miR-29c-3p and the MAPK/JNK signaling pathway.

Abstract

Sanguinarine (SAN), a quaternary benzophenanthridine alkaloid extracted from the root of Papaveraceae plants, has shown antitumour effects in multiple cancer cells. However, the therapeutic effects and the underlying mechanisms of SAN in gastric cancer (GC) remain elusive. In this study, the in vitro proliferation inhibition effect of SAN in GC cells was determined using CCK-8 assay, the in vivo antitumor effect of SAN was evaluated in mice with xenotransplanted tumor. The mechanism underlying the antitumor activity of SAN was explored by gene microarray assay and bioinformatics analysis. The levels of differentially expressed miRNAs and target genes were verified by real-time RT-PCR and immunohistochemistry. SAN inhibited the proliferation of BGC-823 cells in a concentration-dependent manner in vitro and in vivo. The miR-96-5p and miR-29c-3p were significantly upregulated in untreated BGC-823 cells and significantly downregulated in SAN treated cells. The mRNA and protein expression of their target gene MAP4K4 were upregulated in SAN treated xenotransplanted tumors, and pMEK4 and pJNK1 proteins in the MAPK/JNK signaling pathway were also upregulated by SAN. These indicate that SAN may inhibit the proliferation of BGC-823 cells through the inhibition of miR-96-5p and miR-29c-3p expression, and subsequent activation of the MAPK/JNK signaling pathway.

• Authors: Xian-Zhe Dong, Yan Song, Yu-Pan Lu, Yuan Hu, Ping Liu, Lan Zhang
• Journal: Journal of natural medicines (J Nat Med) Vol. 73 Issue 4 Pg. 777-788 (Sep 2019) ISSN: 1861-0293 [Electronic] Japan
• PMID: 31243669 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzophenanthridines
• Intracellular Signaling Peptides and Proteins
• Isoquinolines
• MIRN29a microRNA, human
• MIRN96 microRNA, human
• MicroRNAs
• RNA, Messenger
• sanguinarine
• MAP4K4 protein, human
• Protein Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Benzophenanthridines (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Hep G2 Cells
• Humans
• Intracellular Signaling Peptides and Proteins (drug effects)
• Isoquinolines (pharmacology)
• JNK Mitogen-Activated Protein Kinases (drug effects)
• MAP Kinase Signaling System (drug effects)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (biosynthesis)
• Papaveraceae (chemistry)
• Protein Serine-Threonine Kinases (drug effects)
• RNA, Messenger (biosynthesis)
• Stomach Neoplasms (drug therapy, genetics)
• Xenograft Model Antitumor Assays