Non‐pungent long chain capsaicin‐analogs arvanil and olvanil display better anti‐invasive activity than capsaicin in human small cell lung cancers

The nutritional compound capsaicin inhibits the invasion of many types of human cancers. The clinical development of capsaicin as an anti‐cancer drug is limited due to its unfavorable side effects like burning sensation, stomach cramps, gut pain, and nausea. This study compared the anti‐invasive activity of capsaicin to non‐pungent long chain capsaicin analogs, namely arvanil and olvanil, in human small cell lung cancer cells. Boyden chamber invasion assays revealed that arvanil and olvanil displayed improved anti‐invasive activity relative to capsaicin in human SCLC cells. The results of the Boyden chamber assay were confirmed by the spherical invasion assay, and similar results were obtained. The anti‐invasive activity of arvanil, olvanil and capsaicin were independent of TRPV and CB1 receptors. Furthermore, the anti‐invasive activity of arvanil, olvanil and capsaicin were mediated by the AMPK pathway. Depletion of AMPK levels by siRNA methodology abrogated the anti‐invasive activity of arvanil, olvanil and capsaicin. The non‐pungent capsaicin analogs arvanil and olvanil display improved anti‐invasive activity relative to capsaicin in human SCLC cells. These agents may represent the second generation of capsaicin‐like compounds which are more potent than the parent molecule and have a better side effect profile. Support or Funding Information Funding for our study was supported by the an NIH R15‐AREA Grant (2R15CA161491‐02), AICR Investigator Grant, and a NASA Undergraduate Fellowship to JS.