Apoptotic Activities of : Primary Human Keratinocytes, C-33A, and Human Papillomavirus HeLa Cervical Cancer Lines.

Background: Sanguinarine is a benzophenanthridine alkaloid derived from the root of . Multiple published, preclinical studies have demonstrated that sanguinarine causes apoptosis in human cancer cells. An expert panel of naturopathic doctors identified sanguinarine as a component for consideration in cervical atypia management protocols. Clinical studies have identified positive outcomes when is a constituent of escharotic treatment in cervical atypia management protocols. Therefore, further investigation and development of sanguinarine as a potential cancer treatment is recommended. Thus, the aim of this study is to further elucidate the signaling pathways of sanguinarine-induced cell death.

Methods: Cell cultures of cervical cancer line C-33A (human papillomavirus [HPV] negative), HeLa (HPV positive), and normal primary human keratinocytes were established. Microscopic plate inspection, cell viability, initiator and effector caspase assays were completed in triplicate on C-33A (HPV negative), HeLa (HPV positive), and normal primary human keratinocytes cells exposed to incremental doses of sanguinarine.

Results: Sanguinarine induced dose-dependent cell death in cervical cancer lines as well as in normal human keratinocytes. Microscopic plate inspection confirmed morphologic changes of cell death in normal keratinocytes, C-33A, and HeLa including cell shrinkage, round up, and detachment from plate surface. Caspase assays demonstrated that sanguinarine treatment of C-33A cells resulted in an induction of caspase-3/7 when compared with vehicle-treated controls.

Conclusions: Sanguinarine demonstrates potential as an agent with therapeutic impact because of the capacity to eliminate cancerous cells through apoptosis, the process of programed cell death. Further elucidation of signaling pathways of sanguinarine-induced cell death is necessary when considering sanguinarine as a treatment for cervical cancer.