CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs.
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.
Liao
Ching-Fong
CF
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, ROC.
Luo
Shue-Fen
SF
Shen
Tzu-Yun
TY
Lin
Chin-Huang
CH
Chien
Jung-Tsun
JT
Du
Shin-Yi
SY
Jiang
Ming-Chung
MC
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
D000970:Antineoplastic Agents; D029563:Cellular Apoptosis Susceptibility Protein; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D004317:Doxorubicin; D017239:Paclitaxel