title: Selective enhancing effect of early mitotic inhibitor 1 (Emi1) depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells.
abstract: Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase-promoting complex/cyclosome ubiquitin ligase complex, which ubiquitylates the cell cycle-related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by down-regulating geminin via anaphase-promoting complex/cyclosome activation. At present, anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here, we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA-treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of x-ray irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation.
authors: Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors: Natsumi
authors: N
authors: Shimizu
authors: Nakako Izumi
authors: NI
authors: Nakajima
authors: Takaaki
authors: T
authors: Tsunematsu
authors: Ikuko
authors: I
authors: Ogawa
authors: Hidehiko
authors: H
authors: Kawai
authors: Ryoichi
authors: R
authors: Hirayama
authors: Akira
authors: A
authors: Fujimori
authors: Akiko
authors: A
authors: Yamada
authors: Ryuichi
authors: R
authors: Okayasu
authors: Naozumi
authors: N
authors: Ishimaru
authors: Takashi
authors: T
authors: Takata
authors: Yasusei
authors: Y
authors: Kudo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000378:metabolism; D006801:Humans; D011123:Polyploidy; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C498960:FBXO5 protein, human; D034741:RNA, Small Interfering; C577488:CDC20 protein, human; D004317:Doxorubicin
keywords: Anticancer Drug; Cancer; Cancer Therapy; Cell Cycle; DNA Damage; DNA Synthesis; Radiation Biology
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