Preclinical evaluation of Tanshinones from Salvia miltiorrhiza Bunge on human glioblastoma models in vitro
Piccolo M1, Ferraro M G1, Maione F1, Tammaro C1, Raucci F1, Santamaria R1, Irace C1
1Department of Pharmacy, School of Medicine, University of Naples Federico II, Via Domenico Montesano
49, 80131, Naples, Italy
Medicinal plants and herbal extracts from traditional Chinese medicine are used increasingly commonly worldwide for their benefits to health and quality of life as dietary supplements or as nutraceuticals in functional foods. Among them, Salvia miltiorrhiza Bunge - a natural strong remedy for the treatment of a variety of conditions - is traditionally used for centuries in Asian countries as antioxidant, anticancer, and anti-inflammatory agent. Its pharmacological beneficial effects are mainly ascribed to the presence of lipophilic diterpenoid like-compounds such as dihydrotanshinone (DTA), tanshinone IA (TIA), tanshinone IIA (TIIA) and cryptotanshinone (CRY) that per se are able to penetrate the blood-brain barrier and to inhibit Aβ peptide aggregation, disaggregate amyloid fibrils, and protect neurons from an inflammatory condition. Moreover, several evidences support the hypothesis that tanshinones extracted from the roots (also known as Danshen) of Salvia miltiorrhiza exert significant cytotoxic and/or antiproliferative activity in vitro. Thus, the aim of the present study was to investigate the bioactivity profile of Danshen and its active constituents tanshinone IIA (TIIA) and cryptotanshinone (CRY) in human healthy and cancer models, including glioblastoma and colorectal cancer cells. In this way the anticancer activity of the selected compounds was determined in different cells lines, proving that Danshen and its active constituents were endowed with remarkable and selective inhibitory activities on glioblastoma cell lines LN-229 and U-87 MG (IC50 in the
low micromolar range). Although many advances in antineoplastic therapy have taken place, gliomas have so far shown a poor response to antiproliferative drugs, because of their resistance to most chemotherapeutic agents. However, further experiments are ongoing to give an insight on the molecular mechanisms of action involved in the activation of cell death pathways by tanshinones. Therefore, besides being useful as food complements, preliminary outcome from preclinical evaluations suggest that Salvia miltiorrhiza roots could be considered as a new potential source of bioactive compounds valuable for the development of future anticancer treatments.