Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines.
[Oncogene]
6807162 {6807162:NXKCAY9B} apa 50 1 159629 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-2e4af07d3151dea1f3b61f602f046501%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22NXKCAY9B%22%2C%22library%22%3A%7B%22id%22%3A6807162%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Cheung%20et%20al.%22%2C%22parsedDate%22%3A%222021-03-03%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ECheung%2C%20B.%20B.%2C%20Kleynhans%2C%20A.%2C%20Mittra%2C%20R.%2C%20Kim%2C%20P.%20Y.%2C%20Holien%2C%20J.%20K.%2C%20Nagy%2C%20Z.%2C%20Ciampa%2C%20O.%20C.%2C%20Seneviratne%2C%20J.%20A.%2C%20Mayoh%2C%20C.%2C%20Raipuria%2C%20M.%2C%20Gadde%2C%20S.%2C%20Massudi%2C%20H.%2C%20Wong%2C%20I.%20P.%20L.%2C%20Tan%2C%20O.%2C%20Gong%2C%20A.%2C%20Suryano%2C%20A.%2C%20Diakiw%2C%20S.%20M.%2C%20Liu%2C%20B.%2C%20Arndt%2C%20G.%20M.%2C%20%26%23x2026%3B%20Marshall%2C%20G.%20M.%20%282021%29.%20A%20novel%20combination%20therapy%20targeting%20ubiquitin-specific%20protease%205%20in%20MYCN-driven%20neuroblastoma.%20%3Ci%3EOncogene%3C%5C%2Fi%3E%2C%201%26%23x2013%3B15.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41388-021-01712-w%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41388-021-01712-w%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6807162%26amp%3Bitem_key%3DNXKCAY9B%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20novel%20combination%20therapy%20targeting%20ubiquitin-specific%20protease%205%20in%20MYCN-driven%20neuroblastoma%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Belamy%20B.%22%2C%22lastName%22%3A%22Cheung%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ane%22%2C%22lastName%22%3A%22Kleynhans%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rituparna%22%2C%22lastName%22%3A%22Mittra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Patrick%20Y.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jessica%20K.%22%2C%22lastName%22%3A%22Holien%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zsuzsanna%22%2C%22lastName%22%3A%22Nagy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olivia%20C.%22%2C%22lastName%22%3A%22Ciampa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Janith%20A.%22%2C%22lastName%22%3A%22Seneviratne%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chelsea%22%2C%22lastName%22%3A%22Mayoh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mukesh%22%2C%22lastName%22%3A%22Raipuria%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Satyanarayana%22%2C%22lastName%22%3A%22Gadde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hassina%22%2C%22lastName%22%3A%22Massudi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Iris%20Poh%20Ling%22%2C%22lastName%22%3A%22Wong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Owen%22%2C%22lastName%22%3A%22Tan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrew%22%2C%22lastName%22%3A%22Gong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aldwin%22%2C%22lastName%22%3A%22Suryano%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sonya%20M.%22%2C%22lastName%22%3A%22Diakiw%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bing%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Greg%20M.%22%2C%22lastName%22%3A%22Arndt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tao%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Naresh%22%2C%22lastName%22%3A%22Kumar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olle%22%2C%22lastName%22%3A%22Sangfelt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shizhen%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Murray%20D.%22%2C%22lastName%22%3A%22Norris%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michelle%22%2C%22lastName%22%3A%22Haber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%20R.%22%2C%22lastName%22%3A%22Carter%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20W.%22%2C%22lastName%22%3A%22Parker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Glenn%20M.%22%2C%22lastName%22%3A%22Marshall%22%7D%5D%2C%22abstractNote%22%3A%22Histone%20deacetylase%20%28HDAC%29%20inhibitors%20are%20effective%20in%20MYCN-driven%20cancers%2C%20because%20of%20a%20unique%20need%20for%20HDAC%20recruitment%20by%20the%20MYCN%20oncogenic%20signal.%20However%2C%20HDAC%20inhibitors%20are%20much%20more%20effective%20in%20combination%20with%20other%20anti-cancer%20agents.%20To%20identify%20novel%20compounds%20which%20act%20synergistically%20with%20HDAC%20inhibitor%2C%20such%20as%20suberanoyl%20hydroxamic%20acid%20%28SAHA%29%2C%20we%20performed%20a%20cell-based%2C%20high-throughput%20drug%20screen%20of%2010%2C560%20small%20molecule%20compounds%20from%20a%20drug-like%20diversity%20library%20and%20identified%20a%20small%20molecule%20compound%20%28SE486-11%29%20which%20synergistically%20enhanced%20the%20cytotoxic%20effects%20of%20SAHA.%20Effects%20of%20drug%20combinations%20on%20cell%20viability%2C%20proliferation%2C%20apoptosis%20and%20colony%20forming%20were%20assessed%20in%20a%20panel%20of%20neuroblastoma%20cell%20lines.%20Treatment%20with%20SAHA%20and%20SE486-11%20increased%20MYCN%20ubiquitination%20and%20degradation%2C%20and%20markedly%20inhibited%20tumorigenesis%20in%20neuroblastoma%20xenografts%2C%20and%2C%20MYCN%20transgenic%20zebrafish%20and%20mice.%20The%20combination%20reduced%20ubiquitin-specific%20protease%205%20%28USP5%29%20levels%20and%20increased%20unanchored%20polyubiquitin%20chains.%20Overexpression%20of%20USP5%20rescued%20neuroblastoma%20cells%20from%20the%20cytopathic%20effects%20of%20the%20combination%20and%20reduced%20unanchored%20polyubiquitin%2C%20suggesting%20USP5%20is%20a%20therapeutic%20target%20of%20the%20combination.%20SAHA%20and%20SE486-11%20directly%20bound%20to%20USP5%20and%20the%20drug%20combination%20exhibited%20a%20100-fold%20higher%20binding%20to%20USP5%20than%20individual%20drugs%20alone%20in%20microscale%20thermophoresis%20assays.%20MYCN%20bound%20to%20the%20USP5%20promoter%20and%20induced%20USP5%20gene%20expression%20suggesting%20that%20USP5%20and%20MYCN%20expression%20created%20a%20forward%20positive%20feedback%20loop%20in%20neuroblastoma%20cells.%20Thus%2C%20USP5%20acts%20as%20an%20oncogenic%20cofactor%20with%20MYCN%20in%20neuroblastoma%20and%20the%20novel%20combination%20of%20HDAC%20inhibitor%20with%20SE486-11%20represents%20a%20novel%20therapeutic%20approach%20for%20the%20treatment%20of%20MYCN-driven%20neuroblastoma.%22%2C%22date%22%3A%222021-03-03%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41388-021-01712-w%22%2C%22ISSN%22%3A%221476-5594%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41388-021-01712-w%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-03-03T17%3A57%3A59Z%22%7D%7D%5D%7D
Cheung, B. B., Kleynhans, A., Mittra, R., Kim, P. Y., Holien, J. K., Nagy, Z., Ciampa, O. C., Seneviratne, J. A., Mayoh, C., Raipuria, M., Gadde, S., Massudi, H., Wong, I. P. L., Tan, O., Gong, A., Suryano, A., Diakiw, S. M., Liu, B., Arndt, G. M., … Marshall, G. M. (2021). A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma. Oncogene, 1–15. https://doi.org/10.1038/s41388-021-01712-w Cite