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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Ficus , Lung Neoplasms , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/genetics , Caspases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Latex/metabolism , Gasdermins , Lung Neoplasms/metabolism , Mice, Nude , Tandem Mass Spectrometry , Signal Transduction/physiology , Apoptosis/physiology , Cell Proliferation , Cell Line, TumorABSTRACT
Scientifically elucidating the mode of action of Chinese medicine has become an urgent challenge to Chinese medicine researchers.Opinions on the mode of Chinese medicine effect are active.The scientific hypothesis that additive effect is the key mode of action for Chinese medicine,trigger the scholars and experts in pharmacology field of Chinese medicine to think and contend.The opinion of additive effect provides a new interpretation for mode of action and action characteristics of Chinese medicine.It plays a positive role in the development of pharmacology of Chinese medicine.According to current research results of traditional Chinese medicine (TCM) and clinical cases,this paper made further thinking and summary on the key mode of action for Chinese medicine.The summary is as follows.The diversity of Chinese medicine structure and complexity of Chinese medicine targets determine the complicated mode of action of Chinese medicine.Mode of action for Chinese medicine is complex and variable,which is to adapt to changes in the environment.The genetic diversity of the body receptors due to evolution and the diversity of Chinese medicine and biological complex network control system have determined that a single component of Chinese medicine is more likely to act synergistically by targeting on different targets.From the point of view of Monarch,Minister,Assistant and Guide theory of Chinese medicine,additive effect has limitation.Therefore,just using additive effect is unable to fully explain the Chinese medicine compatible regularity of Monarch,Minister,Assistant and Guide theory.Additive effect is one of action types for Chinese medicine.It is worth to consider if there has any other more important action type for Chinese medicine.
