title: BMI1 is downregulated by the natural compound curcumin, but not by bisdemethoxycurcumin and dimethoxycurcumin.
abstract: The B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) locus encodes a 37-kD protein that is a key regulatory component of the polycomb regulatory complex 1 (PRC1). When overexpressed in various cancer types, the BMI1 protein induces cell growth and promotes tumor growth in vitro and in vivo. Curcumin, a major phytochemical in turmeric (Curcuma longa), inhibits the proliferation and survival of many types of cancer cells, both in vitro and in vivo, and has been reported to reduce BMI1 expression in breast cancer cells. In this study, effects of curcumin and two analogs (bisdemethoxycurcumin and dimethoxycurcumin) on BMI1 expression were evaluated in DLD-1 colorectal cancer cells. Bisdemethoxycurcumin (BDMC) is naturally occurring in turmeric, whereas dimethoxycurcumin (DMC) is a synthetic analog of curcumin. All three compounds reduced cell survival, but only the natural compound downregulated BMI1 protein expression; curcumin significantly reduced BMI1 levels more than bisdemethoxycurcumin and dimethoxycurcumin. In addition, curcumin and BDMC inhibit survival of the DLD-1 colorectal cancer cells by inducing apoptosis, whereas DMC inhibits survival by a mechanism other than apoptosis.
authors.affiliation: Department of Biomedical Laboratory Science, Saint Louis University, St. Louis, Missouri Department of Health Science and Informatics, Saint Louis University, St. Louis, Missouri.
authors.forename: Temitope A
authors.initials: TA
authors.lastname: Adeyeni
authors.affiliation: Department of Biomedical Laboratory Science, Saint Louis University, St. Louis, Missouri.
authors.forename: Natasha
authors.initials: N
authors.lastname: Khatwani
authors.affiliation: Department of Biomedical Laboratory Science, Saint Louis University, St. Louis, Missouri.
authors.forename: KayKay
authors.initials: K
authors.lastname: San
authors.affiliation: Department of Biomedical Laboratory Science, Saint Louis University, St. Louis, Missouri uezekiel@slu.edu.
authors.forename: Uthayashanker R
authors.initials: UR
authors.lastname: Ezekiel
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D036381:Diarylheptanoids; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D008297:Male; D063150:Polycomb Repressive Complex 1 / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C069077:BMI1 protein, human; D018797:Cell Cycle Proteins; D036381:Diarylheptanoids; C116662:PRC1 protein, human; C521105:dimethoxycurcumin; C034786:bisdemethoxycurcumin; D063150:Polycomb Repressive Complex 1; D003474:Curcumin
keywords: Apoptosis; BMI1; colorectal cancer; phytochemical