Document Type
Article
Publication Date
8-22-2023
Publication Title
Biomolecules
Keywords
melanoma, drug discovery, spliceosomal inhibition, BRAF, cell line xenograft, organ histopathology
ISSN
2218-273X
Volume
13
Issue/No.
9
First Page
1276
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
NSUWorks Citation
Velayutham, Sadeeshkumar; Seerattan, Ryan; Sultan, Maab Khalid; Sea, Trisha; Danthurthy, Samaya; Chinnappan, Baskaran; Landi, Jessica; Pearl, Kaitlyn; Singh, Aveta; Smalley, Keiran S. M.; Zaias, Julia; Yong Choi, Jun; and Minond, Dmitriy, "Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice" (2023). HPD Articles. 275.
https://nsuworks.nova.edu/hpd_facarticles/275
ORCID ID
0000-0003-1089-9307, 0000-0001-8218-6440
DOI
10.3390/ biom13091276
Copyright
Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland.
Comments
D.M. and K.S.M.S. designed the study; D.M. obtained funding and wrote the manuscript; S.V. performed animal protocol, histology, and immunostaining, and co-wrote the manuscript; J.Z. performed histopathological evaluation of tumors and co-wrote the manuscript; J.L. and K.P. performed immunofluorescence studies; M.S., B.C., T.S. and S.D. performed animal protocol; J.Y.C. co-wrote the manuscript; A.S. and R.S. synthesized and characterized the compounds for the study. All authors have read and agreed to the published version of the manuscript.