Time-dependent apoptotic responses to vitamin E in precancerous lesions-on- chip models

Abstract

Cervical cancer remains a major global health issue, especially in low- and middle- income countries, with around 660,000 cases and 350,000 deaths in 2022—94% in these regions. Persistent high-risk HPV infection, along with smoking, poor nutrition, inflammation, and immunosuppression, contributes to the progression from LSIL to HSIL and cancer. This study examined how antioxidant treatments—vitamin E and Ialuna®—affect apoptosis in cervical tissue cultured in microfluidic organ-on-a-chip devices, using Bax/Bcl-2 gene expression. Cervical biopsies and a control cell line were cultured in PDMS chips and treated with vitamin E or Ialuna®. Vitamin E triggered an early apoptotic response, especially in LSIL and early HSIL, while Ialuna® induced a slower, sustained effect, notably in HSIL and chronic cervicitis. Bax/Bcl-2 ratios peaked at 144 hours in chronic cervicitis with vitamin E and in HSIL with Ialuna®. This platform offers a promising tool for personalized therapy, supporting a dual antioxidant strategy based on lesion severity and treatment timing.