RNA-directed agent, cordycepin, induces cell death in multiple myeloma cells

British Journal of Haematology
Lisa S ChenVarsha Gandhi

Abstract

Multiple myeloma (MM) is an incurable plasma cell malignancy that is slow-growing, and thus traditional DNA-replication directed chemotherapeutics are ineffective. We hypothesized that those agents that target RNA-directed processes would be successful in MM. To test this postulate, cordycepin, a polyadenylation inhibitor was used as a proof-of-principle towards MM cell lines. Cordycepin accumulated in MM.1S cells as its triphosphate metabolite, 3'dATP and subsequently inhibits RNA synthesis and cell growth. Cell death was via apoptosis induction and over 50% of treated cells were annexin-V positive after 48 h. As a consequence of RNA synthesis inhibition, we hypothesized that specific genes with short half-lives may be downregulated, leading to a reduction in protein. Indeed, a reduction in the transcript levels for MET, a survival gene for MM, was detected as early as 4 h and transcripts were reduced to c. 10% of control after 48 h. Interestingly, no significant change in protein levels was observed for Bcl-2, XIAP, Mcl-1 or survivin. Stabilization of p53 was not observed, and caspases-8, -9 and -3 showed activation following cordycepin treatment but were not required for cell death. Our results suggest that RNA-directed agen...Continue Reading

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Citations

Jul 24, 2012·Investigational New Drugs·Hong Jue LeeAnsgar Brüning
Nov 27, 2009·The Journal of Biological Chemistry·Ying Ying WongCornelia H de Moor
Jan 8, 2010·Molecular Cancer Therapeutics·Jennifer Ann Frey, Varsha Gandhi
Oct 15, 2013·Life Sciences·Hardeep S TuliDharambir Kashyap
Dec 3, 2014·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Shang-Min ChouTang-Long Shen
Dec 2, 2015·Oncology Letters·Xuewen TianLianshi Feng
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Apr 25, 2008·Leukemia Research·Lisa S ChenVarsha Gandhi
Oct 10, 2009·Biochemical Pharmacology·Lisa S ChenVarsha Gandhi
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Jul 4, 2013·European Journal of Pharmacology·Zhao-Lin CaiChu-Hua Li
Jan 1, 2011·Cancers·Christine M Stellrecht, Lisa S Chen
Jun 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peng QinDengXue Lu
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Oct 22, 2010·Journal of Agricultural and Food Chemistry·Ying ChenSeu-Mei Wang

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