Latex derived from Ficus carica L. inhibited the growth of NSCLC by regulating the caspase/gasdermin/AKT signaling pathway

Abstract

Previous studies reported the latex from the fruit of Ficus carica L. (fig) has anti-tumor and antioxidant activities in animal models. However, its active constituents, mechanism of action, and safety remain unknown. The alcohol-precipitated fraction of fig fruit latex (AFFL) was purified and prepared for testing against non-small cell lung cancer (NSCLC). UPLC-TOF-MS/MS was used to examined the components of AFFL. We validated efficacy by researching antitumor phenotypes in vitro and constructing subcutaneous grafts of nude mice with NSCLC, as well as showing the underlying mechanism at the protein level. The results showed that 11 components of AFFL were screened. AFFL significantly inhibited the proliferation, migration, invasion, and clonogenesis of NSCLC cells, promoted cell apoptosis, inhibited tumor growth in A549 xenograft mice, but induced no obvious damage to normal mouse tissues (liver or kidney). Molecular mechanism studies revealed that AFFL could increase Caspase-1 expression in cancer cells by activating the cleavage of Caspase-3 and Caspase-9, inhibiting the activity of Bcl-2, and promoting tumor cell apoptosis. These processes cause gasdermin proteins (GSDMD and GSDME) to be cleaved, releasing N-terminal domain proteins to accumulate and perforate the cell membrane, and promoting tumor cell pyroptosis. In conclusion, our findings suggested that AFFL may promote tumor cell apoptosis and pyroptosis via the Caspase/Gasdermin/AKT signaling pathway and inhibit NSCLC growth in vitro and in vivo, demonstrating that fig latex can be developed as a functional food and drug with anti-NSCLC properties.