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

  • Sadeeshkumar Velayutham
  • , Ryan Seerattan
  • , Maab Sultan
  • , Trisha Seal
  • , Samaya Danthurthy
  • , Baskaran Chinnappan
  • , Jessica Landi
  • , Kaitlyn Pearl
  • , Aveta Singh
  • , Keiran S.M. Smalley
  • , Julia Zaias
  • , Jun Yong Choi
  • , Dmitriy Minond

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1276
JournalBiomolecules
Volume13
Issue number9
DOIs
StatePublished - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Funding

This work was supported by NIH grant R15CA249788 (PI—DM). J.Y.C. and R.S. were supported by NIH SC2 award (SC2GM130470).

ASJC Scopus Subject Areas

  • Biochemistry
  • Molecular Biology

Keywords

  • BRAF
  • cell line xenograft
  • drug discovery
  • melanoma
  • organ histopathology
  • spliceosomal inhibition

Disciplines

  • Biochemistry
  • Molecular Biology

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