title: CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs.
abstract: CSE1L/CAS, a microtubule-associated, cellular apoptosis susceptibility protein, is highly expressed in various cancers. Microtubules are the target of paclitaxel-induced apoptosis. We studied the effects of increased or reduced CAS expression on cancer cell apoptosis induced by chemotherapeutic drugs including paclitaxel. Our results showed that CAS overexpression enhanced apoptosis induced by doxorubicin, 5-fluorouracil, cisplatin, and tamoxifen, but inhibited paclitaxel-induced apoptosis of cancer cells. Reductions in CAS produced opposite results. CAS overexpression enhanced p53 accumulation induced by doxorubicin, 5-fluorouracil, cisplatin, tamoxifen, and etoposide. CAS was associated with alpha-tubulin and beta-tubulin and enhanced the association between alpha-tubulin and beta-tubulin. Paclitaxel can induce G2/M phase cell cycle arrest and microtubule aster formation during apoptosis induction, but CAS overexpression reduced paclitaxel-induced G2/M phase cell cycle arrest and microtubule aster formation. Our results indicate that CAS may play an important role in regulating the cytotoxicities of chemotherapeutic drugs used in cancer chemotherapy against cancer cells.
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, ROC.
authors: Ching-Fong
authors: CF
authors: Liao
authors: Shue-Fen
authors: SF
authors: Luo
authors: Tzu-Yun
authors: TY
authors: Shen
authors: Chin-Huang
authors: CH
authors: Lin
authors: Jung-Tsun
authors: JT
authors: Chien
authors: Shin-Yi
authors: SY
authors: Du
authors: Ming-Chung
authors: MC
authors: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D029563:Cellular Apoptosis Susceptibility Protein / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D029563:Cellular Apoptosis Susceptibility Protein; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D004317:Doxorubicin; D017239:Paclitaxel