title: The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.
abstract: Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells.The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein.Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin.
authors.affiliation: Department of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Alcala de Henares 28871, Madrid, Spain.
authors.forename: Ágata
authors.initials: Á
authors.lastname: Ramos-Torres
authors.affiliation: Department of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Alcala de Henares 28871, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Bort
authors.affiliation: Department of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Alcala de Henares 28871, Madrid, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morell
authors.affiliation: Department of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Alcala de Henares 28871, Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Rodríguez-Henche
authors.affiliation: Department of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Alcala de Henares 28871, Madrid, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Díaz-Laviada
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002211:Capsaicin / Q000302:isolation & purification / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D002211:Capsaicin
keywords: autophagy; capsaicin; prostate cancer; reactive oxygen species