Geraniol induces cooperative interaction of apoptosis and autophagy             to elicit cell death in PC-3 prostate cancer cells.
Geraniol, an acyclic dietary monoterpene, suppresses prostate cancer growth             and enhances docetaxel chemosensitivity in cultured cell or xenograft tumor models.             However, the mechanisms of the geraniol action against prostate cancer are largely             unknown. In this study, we investigated the cellular and molecular mechanisms             of geraniol-induced cell death in PC-3 prostate cancer cells. Among the examined             structurally and functionally similar monoterpenes, geraniol potently induced             apoptosis and autophagy. Although independent processes, apoptosis and autophagy             acted as cooperative partners to elicit geraniol-induced cell death in PC-3 cells.             At a molecular level, geraniol inhibited AKT signaling and activated AMPK signaling,             resulting in mTOR inhibition. Combined treatment of AKT inhibitor and AMPK activator             markedly suppressed cell growth compared to either treatment alone. Our findings             provide insight into future investigations that are aimed at elucidating the role             of apoptosis and autophagy in prostate cancer therapy and at developing anticancer             strategies co-targeting AKT and AMPK.
Department of Physiology, Seoul National University College of                     Medicine, Seoul 110-799, Republic of Korea.
Su-Hwa
SH
Kim
Eun-Jung
EJ
Park
Chae Ryun
CR
Lee
Jung Nyeo
JN
Chun
Nam-Hyuk
NH
Cho
In-Gyu
IG
Kim
Sanghoon
S
Lee
Tae Woo
TW
Kim
Hyun Ho
HH
Park
Insuk
I
So
Ju-Hong
JH
Jeon
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors
D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; D020536:Enzyme Activators; D047428:Protein Kinase Inhibitors; D013729:Terpenes; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C007836:geraniol