LEONARD LOTHSTEIN, Ph.D., M.S., B.A.

Associate Professor
Pathology

Office: Rm 358 Cancer Research Building
Tel: (901) 448-3334
llothstein@uthsc.edu

Education

  • PostDoc, Albert Einstein College of Medicine, Molecular Pharmacology
  • PostDoc, Sloan-Kettering Institute for Cancer Research, Molecular Pharmacology
  • Ph.D., Vanderbilt Univeristy, Molecular Biology
  • B.A., Bowdoin College, Brunswick, ME, Biology

Publications

  1. Díaz Bessone, MI, Berardi, DE, Campodónico, PB, Todaro, LB, Lothstein, L, Bal de Kier Joffé, ED, Urtreger, AJ. Involvement of PKC delta (PKCdelta) in the resistance against different doxorubicin analogs. Breast Cancer Res Treat, 2010.
  2. Du, Z, Fan, M, Kim, JG, Eckerle, D, Lothstein, L, Wei, L, Pfeffer, LM. Interferon-resistant Daudi cell line with a Stat2 defect is resistant to apoptosis induced by chemotherapeutic agents. J Biol Chem, 284 (41), 27808-15, 2009.
  3. Hofmann, PA, Israel, M, Koseki, Y, Laskin, J, Gray, J, Janik, A, Sweatman, TW, Lothstein, L. N-Benzyladriamycin-14-valerate (AD 198): a non-cardiotoxic anthracycline that is cardioprotective through PKC-epsilon activation. J Pharmacol Exp Ther, 323 (2), 658-64, 2007.
  4. Lothstein, L, Savranskaya, L, Sweatman, TW. N-Benzyladriamycin-14-valerate (AD 198) cytotoxicty circumvents Bcr-Abl anti-apoptotic signaling in human leukemia cells and also potentiates imatinib cytotoxicity. Leuk Res, 31 (8), 1085-95, 2007.
  5. He, Y, Liu, J, Grossman, D, Durrant, D, Sweatman, T, Lothstein, L, Epand, RF, Epand, RM, Lee, RM. Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C-delta induces its activation and facilitates mitochondrial targeting of tBid. J Cell Biochem, 101 (5), 1210-21, 2007.
  6. He Y, Liu J, Grossman D, Durrant D, Sweatman T, Lothstein L, Epand RF, Epand RM, Lee RM. Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C-delta induces its activation and facilitates mitochondrial targeting of tBid. Journal of Cellular Biochemistry, 101, 1210-1221, 2007.
  7. Lothstein, L, Savranskaya, L, Barrett, CM, Israel, M, Sweatman, TW. N-benzyladriamycin-14-valerate (AD 198) activates protein kinase C-delta holoenzyme to trigger mitochondrial depolarization and cytochrome c release independently of permeability transition pore opening and Ca2+ influx. Anticancer Drugs, 17 (5), 495-502, 2006.
  8. He, Y, Liu, J, Durrant, D, Yang, HS, Sweatman, T, Lothstein, L, Lee, RM. N-benzyladriamycin-14-valerate (AD198) induces apoptosis through protein kinase C-delta-induced phosphorylation of phospholipid scramblase 3. Cancer Res, 65 (21), 10016-23, 2005.
  9. Bilyeu, JD, Panta, GR, Cavin, LG, Barrett, CM, Turner, EJ, Sweatman, TW, Israel, M, Lothstein, L, Arsura, M. Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines. Mol Pharmacol, 65 (4), 1038-47, 2004.
  10. Panta, GR, Kaur, S, Cavin, LG, Cort├ęs, ML, Mercurio, F, Lothstein, L, Sweatman, TW, Israel, M, Arsura, M. ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol, 24 (5), 1823-35, 2004.
  11. Barrett, CM, Lewis, FL, Roaten, JB, Sweatman, TW, Israel, M, Cleveland, JL, Lothstein, L. Novel extranuclear-targeted anthracyclines override the antiapoptotic functions of Bcl-2 and target protein kinase C pathways to induce apoptosis. Mol Cancer Ther, 1 (7), 469-81, 2002.
  12. Roaten, JB, Kazanietz, MG, Caloca, MJ, Bertics, PJ, Lothstein, L, Parrill, AL, Israel, M, Sweatman, TW. Interaction of the novel anthracycline antitumor agent N-benzyladriamycin-14-valerate with the C1-regulatory domain of protein kinase C: structural requirements, isoform specificity, and correlation with drug cytotoxicity. Mol Cancer Ther, 1 (7), 483-92, 2002.
  13. Barrett CM, Roaten JB, Lewis FL, Sweatman TW, Israel M, Lothstein L.. Drug-induced modulation of protein kinase C (PKC) correlates with circumvention of Bcl-2-mediate inhibition of apoptosis. Molec. Cancer Ther, 1, 469-481, 2002.
  14. Barrett CM, Roaten JB, Lewis FL, Sweatman TW, Israel M, Lothstein L.. Drug-induced modulation of protein kinase C (PKC) correlates with circumvention of Bcl-2-mediate inhibition of apoptosis. Molec. Cancer Ther, 1, 469-481, 2002.
  15. Roaten JB, Kazaneitz MG, Caloca MJ, Bertics PJ, Wiepz GJ, Parrill AL, Rodrigues PJ, Lothstein L, Israel M, Sweatman TW. Protein kinase C inhibition by N-benzyladriamycin-14-valerate (AD 198): Structural requirements, isoform specificity and interaction with the C1-regulatory domain. Molec. Cancer Ther, 1, 483-492, 2002.
  16. Lothstein, L, Israel, M, Sweatman, TW. Anthracycline drug targeting: cytoplasmic versus nuclear--a fork in the road. Drug Resist Updat, 4 (3), 169-77, 2001.
  17. Roaten, JB, Kazanietz, MG, Sweatman, TW, Lothstein, L, Israel, M, Parrill, AL. Molecular models of N-benzyladriamycin-14-valerate (AD 198) in complex with the phorbol ester-binding C1b domain of protein kinase C-delta. J Med Chem, 44 (7), 1028-34, 2001.
  18. Lothstein L, Israel M, Sweatman TW. Anthracycline targeting: Nuclear versus cytoplasmic-A fork in the road. Drug Resistance Updates, 4, 1-9, 2001.
  19. Lothstein, L, Suttle, DP, Roaten, JB, Koseki, Y, Israel, M, Sweatman, TW. Catalytic inhibition of DNA topoisomerase II by N-benzyladriamycin (AD 288). Biochem Pharmacol, 60 (11), 1621-8, 2000.
  20. Pawlik, CA, Israel, M, Sweatman, TW, Lothstein, L. Cellular resistance against the novel hybrid anthracycline N-(2-chloroethyl)-N-nitrosoureidodaunorubicin (AD 312) is mediated by combined altered topoisomerase II and O6-methylguanine-DNA methyltransferase activities. Oncol Res, 10 (4), 209-17, 1998.
  21. Pawlik CA, Israel M, Sweatman TW, Lothstein L.. Multifactorial resistance to the novel hybrid drug 2-chloroethyl nitrosoureidodaunorubicin (AD 312) in murine and human tumor cells. Oncology Research, 10, 209-218, 1998.
  22. Lothstein L, Rodrigues PJ, Sweatman TW, and Israel M.. Intracellular activity, distribution, an metabolism of N-benzyladriamycin-14-valerate (AD 198) are modulated by changes in 14-O-acyl chain length. Anti-Cancer Drugs, 9, 56-66, 1998.
  23. Lothstein, L, Rodrigues, PJ, Sweatman, TW, Israel, M. Cytotoxicity and intracellular biotransformation of N-benzyladriamycin-14-valerate (AD 198) are modulated by changes in 14-O-acyl chain length. Anticancer Drugs, 9 (1), 58-66, 1998.
  24. Lampidis, TJ, Kolonias, D, Podona, T, Israel, M, Safa, AR, Lothstein, L, Savaraj, N, Tapiero, H, Priebe, W. Circumvention of P-GP MDR as a function of anthracycline lipophilicity and charge. Biochemistry, 36 (9), 2679-85, 1997.
  25. Lampidis TJ, Kolonias D, Podoan T, Israel M., Safa AR, Lothstein L, Savaraj N, Tapiero H, Priebe W. Circumvention of P-gp MDR as a function of anthracycline lipophilicity and charge. Biochemistry, 36, 2679-85, 1997.
  26. Lothstein L, Sweatman TW, and Priebe W.. Hydroxylation at C-3 of doxorubicin alters the selected phenotype of cellular drug resistance.. Bioorganic And Medicinal Chemistry, 5, 1807-182=1, 1995.
  27. Lothstein, L, Koseki, Y, Sweatman, TW. P-glycoprotein overexpression in mouse cells does not correlate with resistance to N-benzyladriamycin-14-valerate (AD 198). Anticancer Drugs, 5 (6), 623-33, 1994.
  28. Lothstein L, Hosey LM, Sweatman TW, and Israel M.. N-Benzyladriamycin-14-valerate and drug resistance: correlation of anthracycline structural modifications with intracellular accumulation and distribution in multidrug resistant cells. Oncology Research, 5, 229-2234, 1994.
  29. Lothstein L, Koseki Y, and Sweatman TW.. P-glycoprotein is overexpressed but not involved in resistance to N-benzyladriamycin-14-valerate (AD 198). Anti-Cancer Drugs, 5, 623-633, 1994.
  30. Lothstein, L, Hosey, LM, Sweatman, TW, Koseki, Y, Dockter, M, Priebe, W. N-benzyladriamycin-14-valerate (AD 198)-resistant cells exhibit highly selective cross-resistance to other anthracyclines that circumvent multidrug resistance. Oncol Res, 5 (6-7), 229-34, 1993.
  31. Lothstein, L, Sweatman, TW, Dockter, ME, Israel, M. Resistance to N-benzyladriamycin-14-valerate in mouse J774.2 cells: P-glycoprotein expression without reduced N-benzyladriamycin-14-valerate accumulation. Cancer Res, 52 (12), 3409-17, 1992.
  32. Greenberger LM, Hsu SI-H, Yang C-P, Cohen D, Lothstein L, Han E, Kirschner LS, Piekarz RL, Yu L, and Horwitz SB. A comparison of the Structure, Function, and Expression of P-glycoproteins Encoded by mdr1a and mdr1b in Mouse. Drug Resistance as a Biochemical Target in Cancer Chemotherapy. (Ed. T. Tsuruo and E.Ogawa), 63-95, 1992.
  33. Lothstein, L, Wright, HM, Sweatman, TW, Israel, M. N-benzyladriamycin-14-valerate and drug resistance: correlation of anthracycline structural modification with intracellular accumulation and distribution in multidrug resistant cells. Oncol Res, 4 (8-9), 341-7, 1992.
  34. Hsu SI, Cohen D, Kirschner LS, Lothstein L, Hartstein M, and Horwitz SB. Structual analysis of the mouse mdr 1a (P-glycoprotein) promoter reveals the basis for differential transcript heterogeneity in mulitidrug-resistant J774.2 cells. Molecular And Cellular Biology, 10, 3596-3606, 1990.
  35. Greenberger LM, Lothstein L, and Horwitz SB. Heterogeneous forms of P-glycoprotein in multidrug resistant J774.2 cells. Anticancer Drugs, 191, 263-275, 1989.
  36. Lothstein L, Hsu SI, Horwitz SB, and Greenberger LM. Alternate overexpression of two P-glycoprotein genes is associated with changes in multidrug resistance in J774.2 cell line. Journal of Biological Chemistry, 264, 16054-58, 1989.
  37. Hsu SI, Lothstein SL, Horwitz. Distinct P-glycoprotein precursors are encoded by unique mRNAs which are differentially overexpressed in multidrug mouse cells., 264, 12053-62, 1989.
  38. Slovak ML, Lothstein L, Williams SS, Horwitz SB, and Trent JM.. Analysis of chromosomal alteration and localization of amplified DNA accompanying the development of multidrug resistance. Leukemia, 2, 453-458, 1988.
  39. Horwitz SB, Liao L-L, Greenberger LM, and Lothstein L. Mode of action of taxol and characterization of a multidrug resistant cell line selected with taxol. In Multidrug Resistance (ed., D.Kessel). CRC Press, 109-125, 1988.
  40. Greenberger LM, Lothstein L, Williams SS, Horwitz SB. A family of multidrug resistance-associated glycoproteins: District precursors are overexpressed in independently isolated cells lines. Proceedings of the National Academy of Sciences of the United States of America, 85, 3762-3769, 1988.
  41. Lothstein L and Horwitz SB.. Expression of phenotypic traits following the modulation of colchicines resistance in J774.2 cells. Journal of Cellular Physiology, 127, 253-260, 1986.
  42. Horwitz SB, Lothstein L, Manfredi JJ, Mellado W, Parness J, Roy SN, Schiff PB, Sorbara L., and Zeheb R Taxol. Mechanisms of action and resistance. Ann NY Acad. Sci., 466, 733-744, 1986.