title: Aglycon of rhizochalin from the Rhizochalina incrustata induces apoptosis via activation of AMP-activated protein kinase in HT-29 colon cancer cells.
abstract: Rhizochalin is a two-headed sphingolipid-like compound isolated from the sponge Rhizochalina incrustata. It has been reported that rhizocalin and its derivates have a chemopreventive and chemotherapeutic effect. However, the molecular mechanism of these effects is not understood. Here, we demonstrate that aglycon of rhizochalin (AglRhz) from the Rhizochalina incrustata induces AMP-activated protein kinase (AMPK) phosphorylation, and thereby inhibits mammalian target of rapamycin (mTOR)-p70S6 kinase-extracellular signal-regulated kinase (ERK) signaling and activator protein 1 (AP-1) activity via phosphorylation of Raptor in HT-29 cells. In addition, AglRhz induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP), and DNA fragmentation in HT-29 cells, leads to induction of apoptosis as well as suppression of tumorigenicity of HT-29 cells. Notably, AglRhz inhibits insulin-like growth factor (IGF)-1-induced AP-1 activity and cell transformation in JB6 Cl41 cells. Overall, our findings identify AMPK as an important target protein for mediating the anti-tumor properties of AglRhz in HT-29 colon cancer cells and have important implication for sponges, the most important marine source, in colon cancer.
authors.affiliation: BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501–759, Republic of Korea.
authors.forename: Prem
authors.initials: P
authors.lastname: Khanal
authors.forename: Bong Seok
authors.initials: BS
authors.lastname: Kang
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Yun
authors.forename: Hae-Guk
authors.initials: HG
authors.lastname: Cho
authors.forename: Tatyana Nikolaevna
authors.initials: TN
authors.lastname: Makarieva
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005233:Fatty Alcohols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009792:Oceans and Seas; D010766:Phosphorylation; D008517:Phytotherapy; D028321:Plant Preparations / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011161:Porifera; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D006028:Glycosphingolipids; D028321:Plant Preparations; D013778:Tetrazolium Salts; D013844:Thiazoles; C499268:rhizochalin A; C572755:rhizochalin aglycon; D011065:Poly(ADP-ribose) Polymerases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; C022616:thiazolyl blue