title: Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells.
abstract: Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves of Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae). Experiments were conducted to determine the effects of DMC on cell proliferation, cell-cycle distribution, and programmed cell death in cultures of human colorectal carcinoma HCT116 and LOVO cells. Results showed that DMC inhibited HCT116 and LOVO cell proliferation and induced G(2) /M cell cycle arrest, which was associated with the conversion of microtubule associated protein light chain 3 (LC3)-I-LC3-II, an autophagosome marker, and the incorporation of monodansylcadaverine (MDC), a marker for the acidic compartment of autolysosomes or acidic vesicular organelles. The treatment of HCT116 and LOVO cells using a combination of DMC with an autophagy inhibitor, such as 3-methyladenine (3-MA), beclin 1 siRNA, or atg5 siRNA, suppressed the effect of DMC-mediated anti-proliferation. These results imply that DMC can suppress colorectal carcinoma HCT116 and LOVO cell proliferation through a G(2) /M phase cell-cycle delay, and can induce autophagy, the hallmark of Type II programmed cell death (PCD). Taken together, our results suggest that DMC may be an effective chemotherapeutic agent for HCT116 and LOVO colorectal carcinoma cells.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Korea.
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Evangeline C
authors.initials: EC
authors.lastname: Amor
authors.forename: Jong Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Han-Cheon
authors.initials: HC
authors.lastname: Kim
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D015179:Colorectal Neoplasms; D015870:Gene Expression; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference
chemical_list: C501649:2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; D018797:Cell Cycle Proteins; D047188:Chalcones; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C025946:3-methyladenine; D000225:Adenine