Abstract:
Cervical cancer is a public female health burden, especially in Africa, and is mainly caused by infection with HPV in which unvaccinated cases allow the development of malignancy and ultimately angiogenesis and metastasis. Apoptosis, which is often evaded in cancer, is a popular targeted mechanism of current and potential anti-cancer drugs. However, cytotoxic cervical cancer therapies, such as platinum-based chemo- and radiotherapy, also elicits non-selective and systemic toxicity and temporarily subdues advanced cancers into remission with unexpected relapse. In addition, treatments utilizing an apoptotic anti-cancer approach induce necrosis concomitantly which result in inflammatory side-effects. This necessitates the screening of alternative treatment regimens, such as plant secondary metabolites and their various combinations for discovery of new anti-cancer compounds or unprecedented anti-cancer potentials of old compounds. Therefore, compounds isolated from four Cameroonian plants, namely Cassia arereh, Distemonanthus benthamianus, Echinops gracilis and Rhabdophyllum affine, were screened for their individual cytotoxicities against cervical cancer cells. Compounds that showed sufficient anti-cancer and cancer-selective potentials were then further studied in combination. Initial screening revealed a terpenoid and flavonoid isolated from C. arereh (CAE21) and E. gracilis (EGF25), respectively. CAE21 and EGF25 induced strong apoptotic responses especially in combination with no necrotic response. In addition, CAE21 showed optimal oral bioavailability in silico, although EGF25 did not show the same drug-likability. CAE21 and EGF25 also demonstrated molecular bioactivities of 0.18 and 0.14 as GPCR and nuclear receptor ligands, respectively. Despite the demonstrated anti-cancer potential of CAE21 and EGF25, reproducible effects in more biological cancer models and further elucidation of apoptotic and molecular mechanisms are needed.
