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Taxol Induces bcl-2 Phosphorylation and Death of Prostate Cancer Cells¹

Jefferson Cancer Institute and Jefferson Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107

Treatment of prostate cancer cell lines expressing bcl-2 with taxol induces bcl-2 phosphorylation and programmed cell death, whereas treatment of bcl-2-negative prostate cancer cells with taxol does not induce apoptosis. bcl-2 phosphorylation seems to inhibit its binding to bax since less bax was observed in immunocomplex with bcl-2 in taxol-treated cancer cells. These findings support the use of the anticancer drug taxol for the treatment of bcl-2-positive prostate cancers and other bcl-2-positive malignancies, such as follicular lymphoma.

¹ This work was supported by the Council for Tobacco Research Grant 3496A (to S. H.) and National Cancer Institute Grant CA39860 (to C. M. C.).

² To whom requests for reprints should be addressed, at Jefferson Cancer Institute, 233 South 10th Street, BLSB, Room 1032, Philadelphia, PA 19107-5799.

Received 1/ 5/96. Accepted 2/ 7/96.

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				E. Harper, W. Dang, R. G. Lapidus, and R. I. Garver Jr. Enhanced Efficacy of a Novel Controlled Release Paclitaxel Formulation (PACLIMER Delivery System) for Local-Regional Therapy of Lung Cancer Tumor Nodules in Mice Clin. Cancer Res., December 1, 1999; 5(12): 4242 - 4248. [Abstract] [Full Text] [PDF]

				X.-Z. Wang, J. R. Beebe, L. Pwiti, A. Bielawska, and M. J. Smyth Aberrant Sphingolipid Signaling Is Involved in the Resistance of Prostate Cancer Cell Lines to Chemotherapy Cancer Res., November 1, 1999; 59(22): 5842 - 5848. [Abstract] [Full Text] [PDF]

				A. L. Johnson, J. T. Bridgham, and T. Jensen Bcl-XLONG Protein Expression and Phosphorylation in Granulosa Cells Endocrinology, October 1, 1999; 140(10): 4521 - 4529. [Abstract] [Full Text]

				B. FADEEL, B. ZHIVOTOVSKY, and S. ORRENIUS All along the watchtower: on the regulation of apoptosis regulators FASEB J, October 1, 1999; 13(13): 1647 - 1657. [Abstract] [Full Text]

				G.-J. Zhang, I. Kimijima, M. Onda, M. Kanno, H. Sato, T. Watanabe, A. Tsuchiya, R. Abe, and S. Takenoshita Tamoxifen-induced Apoptosis in Breast Cancer Cells Relates to Down-Regulation of bcl-2, but not bax and bcl-XL, without Alteration of p53 Protein Levels Clin. Cancer Res., October 1, 1999; 5(10): 2971 - 2977. [Abstract] [Full Text] [PDF]

				K. Sugiyama, T. Akiyama, M. Shimizu, T. Tamaoki, C. Courage, A. Gescher, and S. Akinaga Decrease in Susceptibility Toward Induction of Apoptosis and Alteration in G1 Checkpoint Function as Determinants of Resistance of Human Lung Cancer Cells against the Antisignaling Drug UCN-01 (7-Hydroxystaurosporine) Cancer Res., September 1, 1999; 59(17): 4406 - 4412. [Abstract] [Full Text] [PDF]

				K. R. Johnson, K. K. Young, and W. Fan Antagonistic Interplay between Antimitotic and G1-S Arresting Agents Observed in Experimental Combination Therapy Clin. Cancer Res., September 1, 1999; 5(9): 2559 - 2565. [Abstract] [Full Text] [PDF]

				B. Kurdoglu, N. Cheong, J. Guan, B. W. Corn, W. J. Curran Jr., and G. Iliakis Apoptosis as a Predictor of Paclitaxel-induced Radiosensitization in Human Tumor Cell Lines Clin. Cancer Res., September 1, 1999; 5(9): 2580 - 2587. [Abstract] [Full Text] [PDF]

				R. S. DiPaola, M. M. Rafi, V. Vyas, D. Toppmeyer, E. Rubin, J. Patel, S. Goodin, M. Medina, P. Medina, R. Zamek, et al. Phase I Clinical and Pharmacologic Study of 13-cis-Retinoic Acid, Interferon Alfa, and Paclitaxel in Patients With Prostate Cancer and Other Advanced Malignancies J. Clin. Oncol., July 1, 1999; 17(7): 2213 - 2213. [Abstract] [Full Text] [PDF]

				W. Li, J. Fan, D. Banerjee, and J. R. Bertino Overexpression of p21waf1 Decreases G2-M Arrest and Apoptosis Induced by Paclitaxel in Human Sarcoma Cells Lacking Both p53 and Functional Rb Protein Mol. Pharmacol., June 1, 1999; 55(6): 1088 - 1093. [Abstract] [Full Text]

				P. L. Judson, J. M. Watson, P. A. Gehrig, W. C. Fowler Jr., and J. S. Haskill Cisplatin Inhibits Paclitaxel-induced Apoptosis in Cisplatin-resistant Ovarian Cancer Cell Lines: Possible Explanation for Failure ofCombination Therapy Cancer Res., May 1, 1999; 59(10): 2425 - 2432. [Abstract] [Full Text] [PDF]

				S. Gibson, C. Widmann, and G. L. Johnson Differential Involvement of MEK Kinase 1 (MEKK1) in the Induction of Apoptosis in Response to Microtubule-targeted Drugs versus DNA Damaging Agents J. Biol. Chem., April 16, 1999; 274(16): 10916 - 10922. [Abstract] [Full Text] [PDF]

				J. M. Coco Martin, A. Balkenende, T. Verschoor, F. Lallemand, and R. Michalides Cyclin D1 Overexpression Enhances Radiation-induced Apoptosis and Radiosensitivity in a Breast Tumor Cell Line Cancer Res., March 1, 1999; 59(5): 1134 - 1140. [Abstract] [Full Text] [PDF]

				S. K. Manna and B. B. Aggarwal Lipopolysaccharide Inhibits TNF-Induced Apoptosis: Role of Nuclear Factor-{kappa}B Activation and Reactive Oxygen Intermediates J. Immunol., February 1, 1999; 162(3): 1510 - 1518. [Abstract] [Full Text] [PDF]

				P. B. Poommipanit, B. Chen, and Z. N. Oltvai Interleukin-3 Induces the Phosphorylation of a Distinct Fraction of Bcl-2 J. Biol. Chem., January 8, 1999; 274(2): 1033 - 1039. [Abstract] [Full Text] [PDF]

				A.R. Kamer, L. Krebs, S.A. Hoghooghi, and C. Liebow Proliferative and Apoptotic Responses in Cancers With Special Reference To Oral Cancers Critical Reviews in Oral Biology & Medicine, January 1, 1999; 10(1): 58 - 78. [Abstract] [Full Text] [PDF]

				H. M. McDaid and P. G. Johnston Synergistic Interaction between Paclitaxel and 8-Chloro-adenosine 3',5'-Monophosphate in Human Ovarian Carcinoma Cell Lines Clin. Cancer Res., January 1, 1999; 5(1): 215 - 220. [Abstract] [Full Text] [PDF]

				C. D. Scatena, Z. A. Stewart, D. Mays, L. J. Tang, C. J. Keefer, S. D. Leach, and J. A. Pietenpol Mitotic Phosphorylation of Bcl-2 during Normal Cell Cycle Progression and Taxol-induced Growth Arrest J. Biol. Chem., November 13, 1998; 273(46): 30777 - 30784. [Abstract] [Full Text] [PDF]

				M. A. Davis and D. H. Ryan Review Article: Apoptosis in the Kidney Toxicol Pathol, November 1, 1998; 26(6): 810 - 825. [Abstract] [PDF]

				S. F. HAMM-ALVAREZ and M. P. SHEETZ Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney Physiol Rev, October 1, 1998; 78(4): 1109 - 1129. [Abstract] [Full Text] [PDF]

				Z.-B. Hu, M.D. Minden, and E.A. McCulloch Phosphorylation of BCL-2 After Exposure of Human Leukemic Cells to Retinoic Acid Blood, September 1, 1998; 92(5): 1768 - 1775. [Abstract] [Full Text] [PDF]

				J. A. Dominov, J. J. Dunn, and J. B. Miller Bcl-2 Expression Identifies an Early Stage of Myogenesis and Promotes Clonal Expansion of Muscle Cells J. Cell Biol., July 27, 1998; 142(2): 537 - 544. [Abstract] [Full Text] [PDF]

				R. K. Srivastava, A. R. Srivastava, S. J. Korsmeyer, M. Nesterova, Y. S. Cho-Chung, and D. L. Longo Involvement of Microtubules in the Regulation of Bcl2 Phosphorylation and Apoptosis through Cyclic AMP-Dependent Protein Kinase Mol. Cell. Biol., June 1, 1998; 18(6): 3509 - 3517. [Abstract] [Full Text]

				T.-H. Wang, H.-S. Wang, H. Ichijo, P. Giannakakou, J. S. Foster, T. Fojo, and J. Wimalasena Microtubule-interfering Agents Activate c-Jun N-terminal Kinase/Stress-activated Protein Kinase through Both Ras and Apoptosis Signal-regulating Kinase Pathways J. Biol. Chem., February 27, 1998; 273(9): 4928 - 4936. [Abstract] [Full Text] [PDF]

				P. Vilalta, L Zhang, and S. Hamm-Alvarez A novel taxol-induced vimentin phosphorylation and stabilization revealed by studies on stable microtubules and vimentin intermediate filaments J. Cell Sci., January 7, 1998; 111(13): 1841 - 1852. [Abstract] [PDF]

				E. H. Cheng, D. G. Kirsch, R. J. Clem, R. Ravi, M. B. Kastan, A. Bedi, K. Ueno, and J. M. Hardwick Conversion of Bcl-2 to a Bax-like Death Effector by Caspases Science, December 12, 1997; 278(5345): 1966 - 1968. [Abstract] [Full Text]

				S. Wang, J. A. Vrana, T. M. Bartimole, A. J. Freemerman, W. D. Jarvis, L. B. Kramer, G. Krystal, P. Dent, and S. Grant Agents that Down-Regulate or Inhibit Protein Kinase C Circumvent Resistance to 1-beta -D-Arabinofuranosylcytosine-Induced Apoptosis in Human Leukemia Cells that Overexpress Bcl-2 Mol. Pharmacol., December 1, 1997; 52(6): 1000 - 1009. [Abstract] [Full Text]