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Bcl-2 and Bcl-XL Can Differentially Block Chemotherapy-Induced Cell Death
Philip L. Simonian,
Didier A.M. Grillot, and
Gabriel Nuñez
From the Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI.
Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their expression modulates the sensitivity of tumor cells to a wide spectrum of chemotherapeutic agents and  -irradiation. In the present report, we generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if these survival proteins could provide equivalent protection when challenged with chemotherapy or -irradiation. Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection against vincristine and vinblastine whereas Bcl-XL afforded as much as 50% greater cell viability than Bcl-2 against etoposide and teniposide-induced cell death. In addition, Bcl-XL provided significantly greater cell viability than Bcl-2 against methotrexate, fluorouracil, and hydroxyurea, three S-phase specific agents. In apoptosis induced by -irradiation and cisplatin, two antitumor treatments that are cell-cycle phase-nonspecific agents, both Bcl-XL and Bcl-2 conferred similar protection against -irradiation, but Bcl-XL provided better protection than Bcl-2 against cisplatin. These results indicate that Bcl-XL and Bcl-2 confer a differential ability to protect against chemotherapy-induced cell death, which appears to be dependent on the molecular mechanism targeted by the drug rather than its cell-cycle phase specificity.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 1208-1216
© 1997 by The American Society of Hematology.
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