Plantamajoside modulates the proliferation, stemness, and apoptosis of lung carcinoma via restraining p38MAPK and AKT phosphorylation

Plantamajoside (PMS), an active anti-inflammatory component and antioxidant derived from Herba Plantaginis, has been reported to exert a suppressive effect in liver cancer in vivo. In this study, we tested the effects of PMS on the metastatic 95D cell line.

PMS inhibited proliferation, stemness, and migration, and initiated apoptosis in 95D cells, possibly through p38 MAPK and AKT dephosphorylation and mitochondria dysfunction. These findings support the promise of PMS as a prodrug in lung cancer treatment.

95D cells were characterized as most sensitive to PMS across several lung cancer cell lines. Cell viability within 24 h was tested with CCK-8. Different concentrations of PMS (0, 50, 100, and 200 µg/mL) and 5 µg/mL of cisplatin were established for later 24 h treatment. Relative mRNA and protein expression were assessed with PCR and Western blotting. Cell proliferation and stemness were indicated with colony and sphere formation. Cell metastasis was evaluated with wound healing and Transwell. Apoptotic cells and mitochondrial membrane potential were investigated with flow cytometry.

CCK-8 assay showed PMS to inhibit the viability of 95D cells in a dose-dependent manner. PMS decreased colony formation and inhibited stemness in 95D cells. Invasion and migration were also inhibited. Moreover, PMS induced cell apoptosis, and decreased mitochondrial membrane potential. All of these effects were dose dependent. Interestingly, PMS treatment reduced the protein expression of p-p38 MAPK and p-AKT but not that of p38 MAPK and AKT. Conclusions: PMS inhibited proliferation, stemness, and migration, and initiated apoptosis in 95D cells, possibly through p38 MAPK and AKT dephosphorylation and mitochondria dysfunction. These findings support the promise of PMS as a prodrug in lung cancer treatment.