Plant-extracted compounds have been used for centuries in traditional pharmacopeia. Some of them have proven to be excellent drug alternatives for cancer treatment as they target metabolic pathways that are key to cancer cells such as apoptosis, energy-producing catabolic pathways, and the response to oxidative stress. Since some anticancer drugs have been shown to produce dose dependent biologically opposite effects, it is crucial to determine the range of doses for which the compounds have maximum therapeutic benefits. Annona muricata or Graviola is a tropical tree that is common in the Puerto Rican landscape. Although a plethora of studies conducted in vitro and in vivo studies have indeed reported that extracts prepared from the Graviola root, fruit, bark, and leaves possess antiproliferative activities in a large variety of cancer cells, the efficiency of Graviola extracts to curb the progression of head and neck cancers has been overlooked. Furthermore, the bioactivity of Graviola extracts on sane/non-cancerous cells has largely been ignored. The present work reports the in vitro antiproliferative/anticancer behavior of an ethanolic Graviola leaf extract on squamous cell carcinoma cell lines 9 and 25 vs. a sane/non-cancerous human gingival fibroblast cell line-1. Our results show that the Graviola extract induces cell death in the squamous cell carcinoma cell lines at all concentrations tested and a dose-dependent biphasic concentration-dependent/hormetic effect on the fibroblastic cells. This suggests that, at low doses, the phytochemicals present in the prepared Graviola extract could offer potential therapeutic avenues for curbing the progression of head and neck cancers.
Keywords: Anticancer drugs; Cytotoxicity; Graviola; Head and neck squamous cell carcinoma; Hormesis; ROS.