CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs

  • Liao, Ching-Fong (Institute of Cellular and Organismic Biology, Academia Sinica) ;
  • Luo, Shue-Fen (Department of Medicine, Division of Allergy, Immunology and the Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine) ;
  • Shen, Tzu-Yun (Institute of Cellular and Organismic Biology, Academia Sinica) ;
  • Lin, Chin-Huang (Institute of Cellular and Organismic Biology, Academia Sinica) ;
  • Chien, Jung-Tsun (Institute of Cellular and Organismic Biology, Academia Sinica) ;
  • Du, Shin-Yi (Institute of Cellular and Organismic Biology, Academia Sinica) ;
  • Jiang, Ming-Chung (Institute of Cellular and Organismic Biology, Academia Sinica)
  • Received : 2007.07.16
  • Accepted : 2007.09.20
  • Published : 2008.03.31


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-fluorour-acil, 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.


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