Breast cancer causes the most cancer fatalities in women worldwide. Approximately one‐third of breast cancers metastasize, or spread from primary tumors to other tissues, and have a 70% 5‐year mortality rate. Current breast cancer treatments like doxorubicin and paclitaxel become ineffective when breast cancer cells develop multi‐drug resistance and overexpress ATP‐binding cassette transporters, as the transporters cause a substantial efflux of the chemotherapies. Jadomycins, a group of molecules isolated from Streptomyces venezuelae ISP5230, are shown to be cytotoxic against a variety of cancers, especially breast cancer. Furthermore, jadomycins retain their cytotoxic properties in multi‐drug resistant breast cancer cells, as they are not expelled through ATP‐binding cassette transporters. Here, we describe the research that supports the potential use of jadomycins as a novel chemotherapy in the treatment of multi‐drug resistant, metastatic breast cancer. We present the supportive findings, as well as the mechanisms of action investigated thus far. These include copper‐mediated reactive oxygen species generation, aurora B kinase inhibition, and topoisomerase IIα and IIβ inhibition. We also suggest future directions of jadomycin research, which will help to determine if jadomycins can be used as a breast cancer chemotherapy in clinical practice.

ID 14365 Poster Board 355 Background: Inflammatory skin diseases like eczema and psoriasis are common irritating ailments for which there are few effective treatments. Anecdotal stories from the Indigenous L'nu in Cape Breton, NS, Canada suggest that their traditional birch bark oil (BBO) mixture, known as "maskwiomin," demonstrates potential therapeutic effects for the treatment of inflammatory skin diseases. We hypothesize that the mechanisms contributing to the possible beneficial effects of BBO involve anti-oxidant properties, which would ultimately reduce inflammation.Objective: To determine if BBO protects human keratinocytes against oxidative stimuli. Methods and Results:HaCaT human keratinocytes were treated with control cell media, 0.005% v/v BBO, or its vehicle 0.045% v/v dimethyl sulfoxide (DMSO) for 2 or 3 days, followed by 24 h treatment with the oxidative stimulus hydrogen peroxide (H 2 O 2 , 0-3528 mM). MTT assays were performed to quantify subsequent percent cell viability. BBO treatment for 3 days significantly reduced H 2 O 2 -mediated cell death (IC 50 , 3395 ± 205.0 mM) versus DMSO (2729 ± 114.8 mM) and control (2757 ± 113.7 mM). Similar results were observed with BBO treatment after 2 days. Following this, media pre-treatments were repeated for 3 days, with subsequent ROS probe CM-DCFH-DA and H 2 O 2 (588-3528 mM) 1 h treatment. Cytosolic ROS was quantified at lex 485/lem 530 nm. Compared to control and DMSO, BBO-treated cells produced no significant change in the production of ROS. Finally, BBO was tested for the presence of endotoxins, and was found to be below 0.01 EU/mL, which is considered to be endotoxin-free.Conclusions: BBO is endotoxin-free and protects human keratinocytes against the oxidative stimulus H 2 O 2 . However, this effect was not due to a reduction in cytosolic ROS levels. Further experiments are needed to determine the cytoprotective effects including investigation of BBO on mitochondrial ROS. Overproduction of ROS is involved in the pathogenesis of eczema and psoriasis, so it will be important to understand if BBO can mitigate these effects to potentially be used in therapeutic application.