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Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice

Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compoun...

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Autores principales: Velayutham, Sadeeshkumar, Seerattan, Ryan, Sultan, Maab, Seal, Trisha, Danthurthy, Samaya, Chinnappan, Baskaran, Landi, Jessica, Pearl, Kaitlyn, Singh, Aveta, Smalley, Keiran S. M., Zaias, Julia, Choi, Jun Yong, Minond, Dmitriy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526148/
https://www.ncbi.nlm.nih.gov/pubmed/37759675
http://dx.doi.org/10.3390/biom13091276
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author Velayutham, Sadeeshkumar
Seerattan, Ryan
Sultan, Maab
Seal, Trisha
Danthurthy, Samaya
Chinnappan, Baskaran
Landi, Jessica
Pearl, Kaitlyn
Singh, Aveta
Smalley, Keiran S. M.
Zaias, Julia
Choi, Jun Yong
Minond, Dmitriy
author_facet Velayutham, Sadeeshkumar
Seerattan, Ryan
Sultan, Maab
Seal, Trisha
Danthurthy, Samaya
Chinnappan, Baskaran
Landi, Jessica
Pearl, Kaitlyn
Singh, Aveta
Smalley, Keiran S. M.
Zaias, Julia
Choi, Jun Yong
Minond, Dmitriy
author_sort Velayutham, Sadeeshkumar
collection PubMed
description Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to assess the efficacy of these compounds by testing them in A375 cell-line xenograft in nude athymic mice. Animals were randomized into four groups (n = 12/group): 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 thrice a week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results demonstrate the therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.
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spelling pubmed-105261482023-09-28 Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice Velayutham, Sadeeshkumar Seerattan, Ryan Sultan, Maab Seal, Trisha Danthurthy, Samaya Chinnappan, Baskaran Landi, Jessica Pearl, Kaitlyn Singh, Aveta Smalley, Keiran S. M. Zaias, Julia Choi, Jun Yong Minond, Dmitriy Biomolecules Article Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to assess the efficacy of these compounds by testing them in A375 cell-line xenograft in nude athymic mice. Animals were randomized into four groups (n = 12/group): 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 thrice a week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results demonstrate the therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2. MDPI 2023-08-22 /pmc/articles/PMC10526148/ /pubmed/37759675 http://dx.doi.org/10.3390/biom13091276 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Velayutham, Sadeeshkumar
Seerattan, Ryan
Sultan, Maab
Seal, Trisha
Danthurthy, Samaya
Chinnappan, Baskaran
Landi, Jessica
Pearl, Kaitlyn
Singh, Aveta
Smalley, Keiran S. M.
Zaias, Julia
Choi, Jun Yong
Minond, Dmitriy
Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title_full Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title_fullStr Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title_full_unstemmed Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title_short Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice
title_sort novel anti-melanoma compounds are efficacious in a375 cell line xenograft melanoma model in nude mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526148/
https://www.ncbi.nlm.nih.gov/pubmed/37759675
http://dx.doi.org/10.3390/biom13091276
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