A novel method for potentiation of chemotherapy in soft tissue sarcomas with BromAc.

Autor:	Dong L; University of New South Wales, St. George & Sutherland Clinical School Sydney, NSW 2217, Australia., Ke K; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia., Badar S; University of New South Wales, St. George & Sutherland Clinical School Sydney, NSW 2217, Australia.; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia., Mekkawy AH; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia., Akhter J; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia., Pillai K; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia., Carter CJ; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia., Morris DL; University of New South Wales, St. George & Sutherland Clinical School Sydney, NSW 2217, Australia.; Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.; Mucpharm Pty Ltd Australia.
Jazyk:	angličtina
Zdroj:	American journal of translational research [Am J Transl Res] 2022 May 15; Vol. 14 (5), pp. 2894-2909. Date of Electronic Publication: 2022 May 15 (Print Publication: 2022).
Abstrakt:	Single-agent doxorubicin currently forms part of standard care for patients with sarcomas. However, efficacy is limited by the presence of dose-dependent cardiotoxicity and toxicity to renal, hepatic, and neurological systems. Therefore, there is a pressing need for novel drug regimens which can provide increased efficacy and safety. BromAc is a novel drug combination developed as a mucolytic agent which has demonstrated anticancer activity both in vitro and in vivo in several cancers. Here, we investigated the efficacy of BromAc in combination with doxorubicin for four subtypes of sarcoma. Cell proliferation, alongside western blot for a variety of cell cycle, apoptosis, and autophagy biomarkers assays was performed following treatment of cell lines in vitro at various concentrations of BromAc and doxorubicin. The impact of drug treatment on MUC1 and MUC4 levels was assessed through immune-cytological methods. Drug agent synergy was assessed through the Chou-Talalay framework. BromAc treatment in combination with doxorubicin was more efficacious than single-agent doxorubicin, with synergistic effects observed. The immuno-cytological analysis demonstrated significant mucin depletion following treatment with BromAc and doxorubicin used in combination, providing a potential mechanistic underpinning for the observed anticancer effects. Competing Interests: DLM is the co-inventor and assignee of the licence for this study and director of the spin-off sponsor company, Mucpharm Pty Ltd. KK, AHM, JA and KP are employees of Mucpharm Pty Ltd. (AJTR Copyright © 2022.)
Databáze:	MEDLINE
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