Capsaicin and natural capsaicin‐like compounds suppress metastasis in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LAC) accounts for the majority of all non‐small cell lung cancer (NSCLC) cases. A substantial proportion of LAC patients present with local and distant metastasis at the time of their diagnosis. One of the earliest events of the metastatic process is the invasion of malignant cells through the surrounding extracellular basement membrane into the blood and lymph. The long‐term goal of our laboratory is to identify nutrition‐based agents which will suppress the growth and progression of human LACs. Capsaicin is the pungent ingredient of chili peppers. Published reports have revealed that capsaicin inhibits the invasion and metastasis of several types of human cancers including melanoma, prostate cancer, and cholangiosarcoma. However, the clinical application of capsaicin as an anti‐cancer drug is limited by its unpleasant side‐effect profile. This led us to compare the anti‐metastatic activity of capsaicin with natural non‐pungent capsaicin‐like compounds, namely capsiate and capsiconiate. The structure and bioactivity of capsaicin closely resembles capsiate. There are no published reports involving the biological activity of capsiconiate. We measured the anti‐invasive activity of these compounds by two independent invasion assays, namely the Boyden chamber assay and spherical invasion assay. We found that capsaicin and capsiate displayed anti‐invasive activity in three human LAC cell lines. In contrast, capsiconiate did not suppress the invasion of any LAC cell lines. Furthermore, we tested the anti‐metastatic activity of capsaicin in a syngeneic mouse model of metastasis. We observed that the daily dietary administration of capsaicin in AIN‐76A diet (with 5% lipid level) robustly decreased the area metastatic foci (in the lung) relative to vehicle‐treated mice. We investigated the signaling pathway underlying the anti‐metastatic activity of capsaicin. Our results show that capsaicin directly interacts with Src and inhibits Src activation to suppress the metastasis of LAC. The results of our studies may foster the development of novel anti‐metastatic therapies for human LAC.Support or Funding InformationFunding for our study was supported by an NIH R15‐AREA Grant (2R15CA161491‐02) and a NASA Undergraduate Fellowship to NAN.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.