The Natural Chemotherapeutic Capsaicin Activates AMPK through LKB1 Kinase and TRPV1 Receptors in Prostate Cancer Cells

• Published in: Pharmaceutics Vol. 14; no. 2; p. 329
• Main Authors: Sánchez, Belén G, Bort, Alicia, Mora-Rodríguez, José M, Díaz-Laviada, Inés
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-01-2022; MDPI
• Subjects: AMPK; capsaicin; Cell growth; Kinases; LKB1; LNCaP; PC3; Plasmids; Prostate cancer; TRPV1; St Louis Missouri; United States > US; Germany; PC3; prostate cancer; LNCaP; capsaicin; AMPK; DU-145; TRPV1; LKB1
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14020329

The natural bioactive compound capsaicin has been reported to have anticancer activity, although the underlying mechanism of action has not been completely clarified. Herein, we investigated the mechanism whereby capsaicin exerts antitumor effects on prostate cancer cells. We found that capsaicin activated AMP-activated kinase (AMPK) and promoted cell death in the LKB1-expressing prostate cancer cell lines LNCaP and PC3, but not in the liver kinase B1 (LKB1)-null cell line DU-145. Capsaicin treatment stimulated LKB1 phosphorylation and activated AMPK in LKB1-expressing cells. In addition, LKB1 silencing in LNCaP and PC3 cells abrogated capsaicin-induced AMPK activation, while the overexpression of LKB1 by lentiviral infection in DU-145 cells induced capsaicin-triggered AMPK phosphorylation. Moreover, the calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) inhibitor STO-609 did not modify the activation of AMPK induced by capsaicin, suggesting a CaMKK2-independent mechanism. Capsaicin-induced LKB1 phosphorylation was dependent on the transient receptor potential cation channel subfamily V member 1 (TRPV1), since TRPV1 knocked down by shRNA abolished LKB1 and AMPK phosphorylation in LKB1-expressing cells. Altogether, our results showed that capsaicin affected AMPK activity in an LKB1- and TRPV1-dependent fashion, linking TRPV1 with cell fate. These data also suggest that capsaicin may be a rational chemotherapeutic option for prostate tumors.