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MicroRNA-mediated MAPK signaling promotes isoliensinine-induced apoptosis in oral squamous cell carcinoma via the

Zi-Wei Cai1,2, Wei Zhao1, Yu-Ping Gong3

  • 1School of Basic Medicine, Chengdu Medical College Chengdu 610500, Sichuan, China.

American Journal of Cancer Research
|March 23, 2026
PubMed

Insights

Isoliensinine, a natural compound, inhibits oral cancer cell growth by inducing apoptosis and cell cycle arrest. It also modulates microRNAs targeting the MAPK pathway, offering a potential new treatment for oral squamous cell carcinoma (OSCC).

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • Oral squamous cell carcinoma (OSCC) is a prevalent cancer with limited treatment options.
  • Isoliensinine, a bisbenzylisoquinoline alkaloid from Nelumbo nucifera, shows biological activity but its anti-OSCC mechanisms, particularly microRNA (miRNA)-mediated MAPK pathway regulation, are unexplored.

Purpose of the Study:

  • To investigate the anti-OSCC biological activity of isoliensinine.
  • To elucidate the molecular mechanisms underlying isoliensinine's effects on OSCC, focusing on miRNA and MAPK pathway involvement.

Main Methods:

  • Cell viability assays (CCK-8) were performed on OSCC cell lines (HSC-3, HSC-4).
  • mRNA and small RNA sequencing analyzed gene and miRNA expression changes.
  • Gene Ontology (GO) and KEGG pathway analyses identified affected pathways.
  • Flow cytometry assessed reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis, and cell cycle.
  • Western blotting examined key protein expressions related to apoptosis and cell cycle.

Main Results:

  • Isoliensinine inhibited OSCC cell proliferation in a dose- and time-dependent manner.
  • Significant alterations in 1878 genes and 77 miRNAs were observed, primarily impacting the MAPK signaling pathway.
  • Isoliensinine induced apoptosis via ROS-mediated mitochondrial pathways and G2 phase cell cycle arrest.
  • Upregulation of pro-apoptotic proteins (Bax, cleaved caspase-9/-3, cleaved PARP) and MAPK pathway components (p-p38, p-SAPK/JNK) was noted.
  • Downregulation of anti-apoptotic protein (Bcl-2) and cell cycle regulators (p-ERK1/2, Cyclin B1) was observed.

Conclusions:

  • Isoliensinine exhibits significant anti-OSCC activity by inducing apoptosis and cell cycle arrest.
  • The anti-cancer effects are linked to ROS generation, mitochondrial dysfunction, and MAPK pathway activation.
  • Isoliensinine modulates specific miRNAs that target the MAPK pathway, suggesting a novel miRNA-dependent regulatory mechanism in its anti-OSCC action.
Keywords:
IsoliensinineMAPK signaling pathwayMicroRNAapoptosisoral squamous cell carcinomareactive oxygen species

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