E-MTAB-9362
LXR mediated-signalling protects human hair follicles against doxorubicin-induced toxicity ex vivo
Although chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects of cancer treatment, there are still no pharmacological interventions available and there remains an urgent unmet need to identify novel targets for therapy. We hypothesized that selected compounds which enhance ABC transporter activity and thus drug efflux from CIA-affected hair follicle (HF) epithelium may award relative protection from chemotherapy-induced HF toxicity. We found that the LXR agonist T0901317 significantly increased cell survival, attenuated LDH release, caspase-3 activity and DNA double strand breaks (DSBs) in doxorubicin (DOX)-treated outer root sheath keratinocytes (ORS-KCs) in vitro and protected human HFs from DOX-induced apoptosis ex vivo. RNA sequencing was performed to investigate the potential mechanism(s) by which T0901317 may protect against DOX-induced cell survival and apoptosis of ORS-KC.
Although chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects of cancer treatment, there are still no pharmacological interventions available and there remains an urgent unmet need to identify novel targets for therapy. We hypothesized that selected compounds which enhance ABC transporter activity and thus drug efflux from CIA-affected hair follicle (HF) epithelium may award relative protection from chemotherapy-induced HF toxicity. We found that the LXR agonist T0901317 significantly increased cell survival, attenuated LDH release, caspase-3 activity and DNA double strand breaks (DSBs) in doxorubicin (DOX)-treated outer root sheath keratinocytes (ORS-KCs) in vitro and protected human HFs from DOX-induced apoptosis ex vivo. RNA sequencing was performed to investigate the potential mechanism(s) by which T0901317 may protect against DOX-induced cell survival and apoptosis of ORS-KC.