title: SP600125 overcomes antimitotic drug-resistance in cancer cells by increasing apoptosis with independence of P-gp inhibition.
abstract: The purpose of this study was to identify conditions that increase the sensitivity of resistant cancer cells to antimitotic drugs. Using MTS assays, microscopic observation, assessment of cleaved PARP, FACS analysis, and Hoechst staining, we found that the c-Jun N-terminal kinase (Jnk) inhibitor SP600125 (SP) sensitized the antimitotic drug-resistant KBV20C cancer cell line. The sensitization mechanism was independent of p-glycoprotein (P-gp) inhibition. Interestingly, SP-induced sensitization was greater in resistant KBV20C cancer cells than in KB parent cells. The mechanism of SP-induced sensitization involved G2 arrest. KBV20C cells treated with SP and antimitotic drugs were more sensitized than cells treated with SP alone. This suggests that SP can restore sensitization for antimitotic drugs in resistant cancer cells. Our findings may contribute to the development of SP-based combination therapies for patients receiving anti-cancer agents that target microtubules.
authors: Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-764, Republic of Korea.
authors: Ju-Hwa
authors: JH
authors: Kim
authors: College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors: Minji
authors: M
authors: Chae
authors: Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-764, Republic of Korea.
authors: Ae-Ran
authors: AR
authors: Choi
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Hyung
authors: H
authors: Sik Kim
authors: Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-764, Republic of Korea. Electronic address: yoons@ncc.re.kr.
authors: Sungpil
authors: S
authors: Yoon
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology*; D050256:Antimitotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000873:Anthracenes; D050256:Antimitotic Agents; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Antimitotic drugs; Cancer; Chemotherapy; Resistance; SP600125