title: Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway.
abstract: In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer.
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Seula
authors.initials: S
authors.lastname: Han
authors.affiliation: College of Pharmacy, Gachon University, Incheon, Republic of Korea.
authors.forename: Jong Kyu
authors.initials: JK
authors.lastname: Woo
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Yuchae
authors.initials: Y
authors.lastname: Jung
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jeong
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Minsook
authors.initials: M
authors.lastname: Kang
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Young-Ji
authors.initials: YJ
authors.lastname: Yoo
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Hani
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Gachon University, Incheon, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: wykim@sookmyung.ac.kr.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011799:Quinazolines; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C049639:evodiamine
keywords: Breast cancer; Cancer stem-like cells; Evodiamine; Rb