title: p53-dependent and -independent mechanisms are involved in (E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP)-induced apoptosis in HCT116 colon cancer cells.
abstract: (E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP) is a novel synthetic naphthal chalcone derivative. The aim of this study was to investigate the mode of action underlying the antitumor activity of HMP. We found that treatment with HMP potently inhibited the clonogenicity and triggered cell death in HCT116 colon cancer cells. Flow cytometry showed that HMP induced an increase in the population of sub-G0/G1-phase cells. Annexin V binding assay revealed that HMP triggered apoptotic cell death. Furthermore, HMP stimulated the cleavages of caspase-7 and its substrate poly (ADP-ribose) polymerase (PARP). HMP promoted γ-H2AX formation and the production of reactive oxygen species (ROS), and up-regulated expression of the tumor suppressor p53. Interestingly, HMP-induced caspase-7 processing was not completely abrogated in p53-null (p53-/-) HCT116 cells, suggesting that p53-dependent and -independent mechanisms are involved in HMP-induced apoptosis. Egr-1, a zinc finger transcription factor, was upregulated by HMP. Silencing of Egr-1 by shRNA significantly reduced HMP-induced caspase-7 and PARP cleavages, regardless of p53 status. These results suggest that HMP triggers caspase-mediated apoptosis through two distinct mechanisms involving p53-dependent and p53-independent, Egr-1-dependent pathways.
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea; Cancer and Metabolism Institute, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: shinsy@konkuk.ac.kr.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul 02748, Republic of Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: yoongho@konkuk.ac.kr.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053179:Caspase 7 / Q000378:metabolism; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016158:Genes, p53; D045325:HCT116 Cells; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000619667:(E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one; D000970:Antineoplastic Agents; D047188:Chalcones; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D009281:Naphthalenes; D016877:Oxidants; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; C505520:CASP7 protein, human; D053179:Caspase 7
keywords: Apoptosis; Caspase; Egr-1; Naphthal chalcone; Reactive oxygen species; p53