Abstract
Breast carcinomas remain one of the most common forms of cancer among women. Likewise, mammary cancers are one of the leading causes of death in dogs. Among the principal challenges in tumor therapies, resistance to cytotoxic therapeutics represents a major bottleneck in the fight against cancer. The development of novel delivery methods for nitric oxide has fueled the re-emergence of nitric oxide as a potential adjuvant for enhancing sensitivity of cancer cells to traditional therapeutics. More importantly, when delivered under the right conditions, nitric oxide exhibits the capacity to reduce or altogether halt tumor cell proliferation. Here, we present a new class of nitric oxide-releasing pro-drugs using non-cytotoxic S-nitrosothiol nitric oxide donors to deliver nitric oxide in a controlled manner to halt the growth of both human breast and canine mammary carcinoma cells. Research Article Open Access
Highlights
Chemotherapeutic resistance and dose-limiting toxicity are critical limiting factors among current clinical practices for managing human breast and canine mammary cancers [1,2]
To evaluate the impacts of NO released by the dextrancysteine NO donor on canine mammary carcinoma cells, CMT12 cells were exposed to either the dextran-cysteine NO donor or a dextran-cysteine control and growth assays were run to 36h
Given the significance of the impacts of the dextrancysteine NO donor on canine mammary carcinoma cells, we evaluated the impact of the NO donor on a human breast carcinoma line (MCF-7)
Summary
Chemotherapeutic resistance and dose-limiting toxicity are critical limiting factors among current clinical practices for managing human breast and canine mammary cancers [1,2] These limitations have been the impetus for dozens of studies related to adjuvant therapies designed to enhance the tumordirected cytotoxicity of chemotherapeutics. Several isoforms of NO synthase (NOS) which vary in their expression patterns and rates of productivity are responsible for the synthesis of nitric oxide under varying conditions These employ the common substrate, L-arginine, and include: 1) neuronal NOS (nNOS), a calcium dependent form which plays a signaling role in the central nervous system (CNS); 2) endothelial NOS (eNOS), another calcium dependent form involved in cell signaling outside the CNS; and 3) inducible NOS (iNOS), an inducible form with a propensity for producing rapid, high concentration bursts of NO involved in immunological responses [16,17]
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