Velayutham, S.; Seerattan, R.; Sultan, M.; Seal, T.; Danthurthy, S.; Chinnappan, B.; Landi, J.; Pearl, K.; Singh, A.; Smalley, K.S.M.; Zaias, J.; Choi, J.Y.; Minond, D. Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice. Biomolecules2023, 13, 1276.
Velayutham, S.; Seerattan, R.; Sultan, M.; Seal, T.; Danthurthy, S.; Chinnappan, B.; Landi, J.; Pearl, K.; Singh, A.; Smalley, K.S.M.; Zaias, J.; Choi, J.Y.; Minond, D. Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice. Biomolecules 2023, 13, 1276.
Velayutham, S.; Seerattan, R.; Sultan, M.; Seal, T.; Danthurthy, S.; Chinnappan, B.; Landi, J.; Pearl, K.; Singh, A.; Smalley, K.S.M.; Zaias, J.; Choi, J.Y.; Minond, D. Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice. Biomolecules2023, 13, 1276.
Velayutham, S.; Seerattan, R.; Sultan, M.; Seal, T.; Danthurthy, S.; Chinnappan, B.; Landi, J.; Pearl, K.; Singh, A.; Smalley, K.S.M.; Zaias, J.; Choi, J.Y.; Minond, D. Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice. Biomolecules 2023, 13, 1276.
Abstract
Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and 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 determine the therapeutic potential of these compounds by testing them in A375 cell-line derived xenograft in nu/nu mice. Animals were randomized into four groups (n=12/group) to receive subcutaneous administration of vehicle, 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 three times per 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 suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.
Keywords
Melanoma; drug discovery; spliceosomal inhibition; BRAF; cell line xenograft; organ histopathology
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
