Investigating the Clinical Utility of Cell-Permeable Protein Kinase C Delta Peptide Activator in the Setting of Breast Cancer Treatment ID 4053

INTRODUCTION: Protein kinase C delta (PKCδ) activation is known to prevent oxidative damage, elicit cardioprotective effects, and promote antitumor effects via apoptosis. Doxorubicin (DOX) is a potent chemotherapeutic agent that causes significant oxidative damage to cardiomyocytes. This study explores the interaction of PKCδ activator (PKCδ+) with DOX in breast cancer cells (MCF7) and cardiomyocytes (H9C2) to identify the clinical utility of PKCδ+. METHODS: MCF7 and H9C2 cells were plated onto 96-well plates and pretreated with dual conjugated N-terminous myristic acid (Myr) and trans-activator of transcription peptide (Tat) PKCδ+ peptide (0.5–20 micromolar), DOX (5–50 micromolar), a combination of PKCδ+ and DOX, or untreated control for 37 minutes. Cell viability was assessed by light microscopy/spectrophotometric analysis. Data were analyzed using the Student t-test. RESULTS: DOX (n=4, P <.05) only reduced MCF7 viability by 2% at maximum dosage of 50 micromolar and significantly decreased viability in H9C2 cells at doses of 10–50 micromolar up to 28%. PKCδ+ (n=4, P <.05) significantly and dose-dependently reduced MCF7 viability at doses of 4–20 micromolar up to 39%, while preserving H9C2 viability. PKCδ+ (2–5 micromolar) provided protective effects in MCF7 and H9C2 cells co-treated with DOX (20–30 micromolar), significantly improving viability in MCF7 at doses of up to 42%. CONCLUSIONS/IMPLICATIONS: In the setting of oxidative stress, PKCδ+ elicits protective effects to both cell types, while in its absence, it provides potent anticancer effects without harming cardiac tissue. This suggests that PKCδ+ may be used as a substitute for DOX, as opposed to adjuvant therapy in breast cancer treatment.