Resumen:
Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment
of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the
mechanisms that drive these skin adverse events are not clearly understood. In the present study,
we demonstrated, by using both primary epidermal keratinocytes (NHEK) and a 3D epidermis
model, that paclitaxel impairs different cellular processes: paclitaxel increased the release of IL-1α,
IL-6, and IL-8 inflammatory cytokines, produced reactive oxygen species (ROS) release and apoptosis, and reduced the endothelial tube formation in the dermal microvascular endothelial cells
(HDMEC). Some of the mechanisms driving these adverse skin events in vitro are mediated by the
activation of toll-like receptor 4 (TLR-4), which phosphorylate transcription of nuclear factor kappa
B (NF-κb). This is the first study analyzing paclitaxel effects on healthy human epidermal cells with
an epidermis 3D model, and will help in understanding paclitaxel’s effects on the skin.