Hurley John D, Akers Austin T, Friedman Jamie R, Nolan Nicholas A, Brown Kathleen C, Dasgupta Piyali
a Department of Pharmacology, Physiology, and Toxicology , Joan C. Edwards School of Medicine, Marshall University , Huntington , WV , USA.
Cell Adh Migr. 2017 Jan 2;11(1):80-97. doi: 10.1080/19336918.2016.1187368. Epub 2016 May 19.
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 was 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.
营养化合物辣椒素可抑制多种人类癌症的侵袭。由于其存在如灼烧感、胃痉挛、肠道疼痛和恶心等不良副作用，辣椒素作为抗癌药物的临床开发受到限制。本研究比较了辣椒素与无辛辣味的长链辣椒素类似物（即阿伐尼尔和奥伐尼尔）在人小细胞肺癌细胞中的抗侵袭活性。博伊登小室侵袭试验表明，在人小细胞肺癌细胞中，阿伐尼尔和奥伐尼尔相对于辣椒素表现出更强的抗侵袭活性。博伊登小室试验的结果通过球形侵袭试验得到了证实，且获得了相似的结果。阿伐尼尔、奥伐尼尔和辣椒素的抗侵袭活性与瞬时受体电位香草酸亚型1（TRPV）和大麻素受体1（CB1）无关。此外，阿伐尼尔、奥伐尼尔和辣椒素的抗侵袭活性是由腺苷酸活化蛋白激酶（AMPK）途径介导的。采用小干扰RNA（siRNA）方法降低AMPK水平可消除阿伐尼尔、奥伐尼尔和辣椒素的抗侵袭活性。在人小细胞肺癌细胞中，无辛辣味的辣椒素类似物阿伐尼尔和奥伐尼尔相对于辣椒素表现出更强的抗侵袭活性。这些药物可能代表了第二代辣椒素样化合物，它们比母体分子更有效，且副作用更小。
