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Cancer Biology & Therapy Volume 10, 2010 - Issue 6
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Research Paper

Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma

Evidence for p53-transcription-dependent and -independent pathways

Manujendra N. Saha Division of Molecular and Cellular Biology, Toronto General Hospital Research Institute; Dept. of Laboratory Medicine & Pathobiology, University of Toronto
,
Hua Jiang Dept. of Laboratory Medicine & Pathobiology, University of Toronto; Department of Laboratory Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University, Shanghai, China
&
Hong Chang Division of Molecular and Cellular Biology, Toronto General Hospital Research Institute; Dept. of Laboratory Medicine & Pathobiology, University of Toronto; Dept. of Laboratory Hematology and Medical Oncology, University Health Network, Toronto, Ontario, CanadaCorrespondence[email protected]
Pages 567-578 | Published online: 15 Sep 2010

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Qi Zhang & Hua Lu. (2010) Nutlin's two roads toward apoptosis. Cancer Biology & Therapy 10:6, pages 579-581.
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Jialiang Zheng, Fenglin Miao, Zhao Wang, Yuan Ma, Zhenhang Lin, Yaqin Chen, Xu Kong, Yue Wang, Aobo Zhuang, Ting Wu & Wengang Li. (2023) Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy. Life Sciences 327, pages 121832.
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Chuting Li, Ru Su, Xiuyuan Wang, Guiping Huang, Yanjun Liu, Juhua Yang, Zhao Yin, Chunming Gu & Jia Fei. (2022) Discovery of the oncogenic MDM2, a direct binding target of berberine and a potential therapeutic, in multiple myeloma. Functional & Integrative Genomics 22:5, pages 1031-1041.
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Omar Faruq, Davidson Zhao, Mariusz Shrestha, Andrea Vecchione, Eldad Zacksenhaus & Hong Chang. (2022) Targeting an MDM2/MYC Axis to Overcome Drug Resistance in Multiple Myeloma. Cancers 14:6, pages 1592.
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Lucia Haronikova, Ondrej Bonczek, Pavlina Zatloukalova, Filip Kokas-Zavadil, Martina Kucerikova, Philip J. Coates, Robin Fahraeus & Borivoj Vojtesek. (2021) Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?. Cellular & Molecular Biology Letters 26:1.
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Lukas John, Maria Theresa Krauth, Klaus Podar & Marc-Steffen Raab. (2021) Pathway-Directed Therapy in Multiple Myeloma. Cancers 13:7, pages 1668.
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Ignacio J. Cardona-Benavides, Cristina de Ramón & Norma C. Gutiérrez. (2021) Genetic Abnormalities in Multiple Myeloma: Prognostic and Therapeutic Implications. Cells 10:2, pages 336.
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Radhika Bansal, Sagar Rakshit, Weiguo Han & Shaji Kumar. (2021) Modulation of Apoptosis Pathways in the Biology and Treatment of Multiple Myeloma. Oncology & Haematology 17:1, pages 48.
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Ivie L. Conlon, Brandon Drennen, Maryanna E. Lanning, Samuel Hughes, Rebecca Rothhaas, Paul T. Wilder, Alexander D. MacKerellJr.Jr. & Steven Fletcher. (2020) Rationally Designed Polypharmacology: α‐Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl‐1 and HDM2. ChemMedChem 15:18, pages 1691-1698.
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Higor Oliveira Ribeiro, Alane Pereira Cortez, Renato Ivan Ávila, Artur Christian Garcia Silva, Flávio Silva Carvalho, Ricardo Menegatti, Luciano Morais Lião & Marize Campos Valadares. (2020) Small‐molecule MDM2 inhibitor LQFM030‐induced apoptosis in p53‐null K562 chronic myeloid leukemia cells. Fundamental & Clinical Pharmacology 34:4, pages 444-457.
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Erin Flynt, Kamlesh Bisht, Vinidhra Sridharan, María Ortiz, Fadi Towfic & Anjan Thakurta. (2020) Prognosis, Biology, and Targeting of TP53 Dysregulation in Multiple Myeloma. Cells 9:2, pages 287.
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Vidya Ramakrishnan & Donald E. Mager. (2018) Pharmacodynamic Models of Differential Bortezomib Signaling Across Several Cell Lines of Multiple Myeloma. CPT: Pharmacometrics & Systems Pharmacology 8:3, pages 146-157.
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Katarina K. Jovanović, Guillaume Escure, Jordane Demonchy, Alexandre Willaume, Zoe Van de Wyngaert, Meryem Farhat, Paul Chauvet, Thierry Facon, Bruno Quesnel & Salomon Manier. (2019) Deregulation and Targeting of TP53 Pathway in Multiple Myeloma. Frontiers in Oncology 8.
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Shaji K. Kumar. (2019) Targeted Management Strategies in Multiple Myeloma. The Cancer Journal 25:1, pages 59-64.
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Lukasz Skalniak, Justyna Kocik, Justyna Polak, Anna Skalniak, Monika Rak, Agnieszka Wolnicka-Glubisz & Tad Holak. (2018) Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells. Cancers 10:11, pages 396.
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Lisa J. Crawford & Alexandra E. Irvine. 2018. Ubiquitination Governing DNA Repair - Implications in Health and Disease. Ubiquitination Governing DNA Repair - Implications in Health and Disease.
James A. McCubrey, Kvin Lertpiriyapong, Timothy L. Fitzgerald, Alberto M. Martelli, Lucio Cocco, Dariusz Rakus, Agnieszka Gizak, Massimo Libra, Melchiorre Cervello, Guiseppe Montalto, Li V. Yang, Stephen L. Abrams & Linda S. Steelman. (2017) Roles of TP53 in determining therapeutic sensitivity, growth, cellular senescence, invasion and metastasis. Advances in Biological Regulation 63, pages 32-48.
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Ana Herrero, Elizabeta Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski & Norma Gutiérrez. (2016) Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma. International Journal of Molecular Sciences 17:12, pages 2003.
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Lisa J. Crawford, Gordon Anderson, Cliona K. Johnston & Alexandra E. Irvine. (2016) Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. Oncotarget 7:43, pages 70481-70493.
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Kimo C. Stine, Elizabeth C. Wahl, Lichu Liu, Robert A. Skinner, Jaclyn VanderSchilden, Robert C. Bunn, Corey O. Montgomery, James Aronson, David L. Becton, Richard W. Nicholas, Christopher J. Swearingen, Larry J. Suva & Charles K. Lumpkin. (2016) Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity. Journal of Orthopaedic Research 34:10, pages 1716-1724.
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Mariana F da Mota, Alane P Cortez, Polyana L Benfica, Bruna dos S Rodrigues, Thalyta F Castro, Larissa M Macedo, Carlos H Castro, Luciano M Lião, Flávio S de Carvalho, Luiz A S Romeiro, Ricardo Menegatti, Hugo Verli, Bianca Villavicencio & Marize C Valadares. (2016) Induction of apoptosis in Ehrlich ascites tumour cells via p53 activation by a novel small-molecule MDM2 inhibitor – LQFM030. Journal of Pharmacy and Pharmacology 68:9, pages 1143-1159.
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Susanne Lub, Ken Maes, Eline Menu, Elke De Bruyne, Karin Vanderkerken & Els Van Valckenborgh. (2015) Novel strategies to target the ubiquitin proteasome system in multiple myeloma. Oncotarget 7:6, pages 6521-6537.
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Małgorzata Zając & Krzysztof Giannopoulos. (2015) Mutacje TP53 w nowotworach hematologicznych. Acta Haematologica Polonica 46:5, pages 327-338.
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Jian-Jun Zhao, Zhang-Bo Chu, Yu Hu, Jianhong Lin, Zhongqiu Wang, Meng Jiang, Ming Chen, Xujun Wang, Yue Kang, Yangsheng Zhou, Triona Ni Chonghaile, Melanie E. Johncilla, Yu-Tzu Tai, Jin Q. Cheng, Antony Letai, Nikhil C. Munshi, Kenneth C. Anderson & Ruben D. Carrasco. (2015) Targeting the miR-221–222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer Research 75:20, pages 4384-4397.
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Saura C. Sahu, Jiwen Zheng, Jeffrey J. Yourick, Robert L. Sprando & Xiugong Gao. (2015) Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles. Journal of Applied Toxicology 35:10, pages 1160-1168.
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P J Teoh, T H Chung, S Sebastian, S N Choo, J Yan, S B Ng, R Fonseca & W J Chng. (2014) p53 haploinsufficiency and functional abnormalities in multiple myeloma. Leukemia 28:10, pages 2066-2074.
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SUN-YOUNG LEE, HYUN CHUL CHOI, YUN-JEONG CHOE, SEOK JOON SHIN, SUG HYUNG LEE & HO-SHIK KIM. (2014) Nutlin-3 induces BCL2A1 expression by activating ELK1 through the mitochondrial p53-ROS-ERK1/2 pathway. International Journal of Oncology 45:2, pages 675-682.
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M N Saha, Y Chen, M-H Chen, G Chen & H Chang. (2014) Small molecule MIRA-1 induces in vitro and in vivo anti-myeloma activity and synergizes with current anti-myeloma agents. British Journal of Cancer 110:9, pages 2224-2231.
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Seung-Wook Chi. (2014) Structural insights into the transcription-independent apoptotic pathway of p53. BMB Reports 47:3, pages 167-172.
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Kian Hoe Khoo, Chandra S. Verma & David P. Lane. (2014) Drugging the p53 pathway: understanding the route to clinical efficacy. Nature Reviews Drug Discovery 13:3, pages 217-236.
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P. J. Teoh & W. J. Chng. (2014) p53 Abnormalities and Potential Therapeutic Targeting in Multiple Myeloma. BioMed Research International 2014, pages 1-9.
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Chunhua Wan, Jian Chen, Baoying Hu, Huifei Zou, Aihong Li, Aihang Guo & Junkang Jiang. (2014) Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury. Journal of Neuroscience Research 92:1, pages 1-12.
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Jahangir Abdi, Guoan Chen & Hong Chang. (2013) Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget 4:12, pages 2186-2207.
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Manujendra N Saha, Lugui Qiu & Hong Chang. (2013) Targeting p53 by small molecules in hematological malignancies. Journal of Hematology & Oncology 6:1.
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Manujendra N. Saha, Hua Jiang, Yijun Yang, Donna Reece & Hong Chang. (2013) PRIMA-1Met/APR-246 Displays High Antitumor Activity in Multiple Myeloma By Induction of p73 and Noxa. Molecular Cancer Therapeutics 12:11, pages 2331-2341.
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Lisa J. Crawford & Alexandra E. Irvine. (2013) Targeting the ubiquitin proteasome system in haematological malignancies. Blood Reviews 27:6, pages 297-304.
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Xinghua Chen, Zhilong Ren, Wei Liang, Dongqing Zha, Yipeng Liu, Cheng Chen, Pravin C. Singhal & Guohua Ding. (2013) c-Abl mediates angiotensin II-induced apoptosis in podocytes. Journal of Molecular Histology 44:5, pages 597-608.
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Manujendra N Saha, Yijun Yang & Hong Chang. (2012) Targeting p53 by small molecule p53 activators in multiple myeloma. Journal of Hematology & Oncology 5:S1.
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Jie He, Zhengtang Qi, Yuhui Su, Qiang He, Jingxia Liu, Lu Yu, Omar S. Al-Attas, Tajamul Hussain, Edgardo Tan De Rosas, Liu Ji & Shuzhe Ding. (2012) Pifithrin-μ increases mitochondrial COX biogenesis and MnSOD activity in skeletal muscle of middle-aged mice. Mitochondrion 12:6, pages 630-639.
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Merav Leiba, Jana Jakubikova, Steffen Klippel, Constantine S. Mitsiades, Teru Hideshima, Yu-Tzu Tai, Adi Leiba, Mark Pines, Paul G. Richardson, Arnon Nagler & Kenneth C. Anderson. (2012) Halofuginone inhibits multiple myeloma growth in vitro and in vivo and enhances cytotoxicity of conventional and novel agents. British Journal of Haematology 157:6, pages 718-731.
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K. Aziz, S. Nowsheen, G. Pantelias, G. Iliakis, V.G. Gorgoulis & A.G. Georgakilas. (2012) Targeting DNA damage and repair: Embracing the pharmacological era for successful cancer therapy. Pharmacology & Therapeutics 133:3, pages 334-350.
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Jae-Sun Shin, Ji-Hyang Ha, Fahu He, Yutaka Muto, Kyoung-Seok Ryu, Ho Sup Yoon, Sunghyun Kang, Sung Goo Park, Byoung Chul Park, Sang-Un Choi & Seung-Wook Chi. (2012) Structural insights into the dual-targeting mechanism of Nutlin-3. Biochemical and Biophysical Research Communications 420:1, pages 48-53.
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Manujendra N. Saha, Hua Jiang, Yijun Yang, Xiaoyun Zhu, Xiaoming Wang, Aaron D. Schimmer, Lugui Qiu & Hong Chang. (2012) Targeting p53 via JNK Pathway: A Novel Role of RITA for Apoptotic Signaling in Multiple Myeloma. PLoS ONE 7:1, pages e30215.
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Rebecca Voltan, Maria Grazia di Iasio, Raffaella Bosco, Nicola Valeri, Yuri Pekarski, Mario Tiribelli, Paola Secchiero & Giorgio Zauli. (2011) Nutlin-3 Downregulates the Expression of the Oncogene TCL1 in Primary B Chronic Lymphocytic Leukemic Cells . Clinical Cancer Research 17:17, pages 5649-5655.
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Manujendra N. Saha, Hua Jiang, Asuka Mukai & Hong Chang. (2010) RITA Inhibits Multiple Myeloma Cell Growth through Induction of p53-Mediated Caspase-Dependent Apoptosis and Synergistically Enhances Nutlin-Induced Cytotoxic Responses. Molecular Cancer Therapeutics 9:11, pages 3041-3051.
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