Anti‐invasive activity of capsaicin and non‐pungent capsaicin analogs in human SCLC

Abstract

Small cell lung cancer (SCLC) is the most aggressive lung malignancy. A majority of SCLC patients show extrapulmonary metastasis at the time of their presentation. The common sites of SCLC metastasis are bone and the brain. The invasion of malignant cells to the neighboring blood vessels and lymph nodes is a key step of metastasis. Recent data indicate that dietary compounds (by themselves or in combination with standard chemotherapy) reduce invasion and metastasis of several human cancers. Capsaicin is the pungent ingredient of chili peppers. Recent studies have shown that capsaicin inhibits the invasion and metastasis of several types of human cancers including melanoma, prostate cancer and cholangiosarcoma. We tested the anti‐invasive activity of capsaicin, as well as two non‐pungent capsaicin analogs, olvanil and arvanil, in human SCLC using the Boyden chamber assay and spherical invasion assay. We found that olvanil and arvanil possess greater anti‐invasive activity than capsaicin. The biological activity of capsaicin is mediated by transient receptor potential vanilloid (TRPV) receptors on target cells. However, arvanil and olvanil bind to both TRPV and cannabinoid receptors. Boyden chamber and spherical invasion assay revealed that the anti‐invasive effects of capsaicin, olvanil and arvanil were independent of both TRPV and cannabinoid receptors. The capsaicin analogs olvanil and arvanil may prove useful for the management and treatment of SCLC metastasis.Support or Funding InformationFunding for our study was supported by the an NIH R15‐AREA Grant (1R15HL113681‐01A1), AICR Investigator Grant, and a NASA Undergraduate Fellowship to ATA.