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BCL 2 and BCL xL are key determinants of resistance to antitubulin chemotherapeutics in melanoma cells
Author(s) -
Watanabe Ayano,
Yasuhira Shinji,
Inoue Tsuyoshi,
Kasai Shuya,
Shibazaki Masahiko,
Takahashi Kazuhiro,
Akasaka Toshihide,
Masuda Tomoyuki,
Maesawa Chihaya
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12185
Subject(s) - paclitaxel , tubulin , apoptosis , melanoma , microtubule , mitosis , mcl1 , cell culture , chemistry , nocodazole , cancer research , biology , cell , microbiology and biotechnology , chemotherapy , downregulation and upregulation , biochemistry , cytoskeleton , genetics , gene
Malignant melanoma is refractory to various chemotherapeutics including antitubulin agents such as paclitaxel. Previous studies have suggested a link between β III ‐tubulin overexpression and paclitaxel resistance through alterations in the properties of the mitotic spindle. We found that paclitaxel treatment induced temporary mitotic arrest in 7 melanoma cell lines irrespective of the β III ‐tubulin level, suggesting that β III ‐tubulin had no significant influence on spindle properties. On the other hand, the amount of BCL 2, an anti‐apoptotic protein, was well correlated with paclitaxel resistance. Treatment of the paclitaxel‐resistant cell lines with ABT ‐737, an inhibitor of BCL 2 and BCL xL, or simultaneous knock‐down of BCL 2 and BCL xL dramatically increased the cells’ sensitivity, while knock‐down of MCL 1, another member of the BCL 2 family, had only a minimal effect. Our results suggest that the paclitaxel sensitivity of melanoma cells is attributable to apoptosis susceptibility rather than a change in spindle properties and that BCL 2 and BCL xL play a pivotal role in the former.