Marine fungus-derived alkaloid inhibits the growth and metastasis of gastric cancer via targeting mTORC1 signaling pathway

Gastric cancer (GC) is a highly aggressive and deadly disease worldwide. Given the limitations of current treatments, it is crucial to discover more effective antitumor drugs. Here, we demonstrated that arthpyrone M (Art-M), a novel 4-hydroxy-2-pyridone alkaloid derived from the marine fungus Arthrinium arundinis, inhibited the proliferation, invasion and migration of GC both in vivo and in vitro. The underlying mechanism of Art-M in GC cells was explored by RNA-sequencing analysis, qRT-PCR and immunoblotting, which demonstrated that Art -M significantly suppressed the mTORC1 pathway by decreasing phosphorylated mTOR and p70S6K. Moreover, Art-M feedback increased the activities of AKT and ERK. Co-immunoprecipitation and immunoblotting analysis revealed that Art-M induced dissociation of Raptor from mTOR and promoted Raptor degradation, leading to the inhibition of mTORC1 activity. Art-M was identified as a novel and potent mTORC1 antagonist. Furthermore, Art-M enhanced GC cell sensitivity to apatinib, and the combination of Art-M and apatinib showed better efficacy in the treatment of GC. Taken together, these results demonstrate that Art-M is a promising candidate drug for the treatment of GC by suppressing the mTORC1 pathway.

Automated summary

A novel compound named arthpyrone M (Art-M) derived from marine fungus Arthrinium arundinis showed potential antitumor activity against gastric cancer (GC) by inhibiting cell proliferation, invasion, and migration. The mechanism was found to be through suppressing the mTORC1 pathway. Additionally, Art-M enhanced the sensitivity of GC cells to apatinib and showed better efficacy when used in combination.