Anti-proliferative effect of leaf phytochemicals of soursop (Annona muricata L.) against human osteosarcoma in vitro

Abstract

Abstract Soursop (Annona muricata) is being used in treating various types of cancers and there is no report on effect of soursop leaf phytochemicals against osteosarcoma. Current study identified 28 metabolites from ethyl acetate leaf (EAL) extract through GC-MS chemoprofiling and subjected to in silico analysis against the potential protein target, Platelet Derived Growth Factor Receptor α (PDGFRA) of osteosarcoma, including Absorption, Distribution, Metabolism, and Excretion and Toxicity (ADMET) analysis to identify possible hit compounds. This resulted in three hit leaf bioactives namely, 2’- hydroxy-5’-methyl chalcone, linoleic acid and annonacin showing good binding affinity with a docking score of -7.4, -7.0 and – 6.9 kcal/mol respectively. With ADMET analysis, 2’- hydroxy-5’-methyl chalcone and linoleic acid obeyed Lipkinsi’s rule of five, whereas annonacin showed slight violation. Among the three docked complexes, annonacin exhibited good stability during molecular dynamic simulation performed with PDGFRA. Hence, concentration of the key marker compound, annonacin in EAL concentrate is found to be 5.032± 0.13 mg/g of leaf sample. Further, EAL concentrate exhibited cytotoxicity (IC50 value) on MG-63 osteosarcoma cells in vitro for concentrations ranging from 10 to 25 µg/mL and nuclear imaging of osteoblast cells treated with EAL concentrate at 25 µg/mL concentration exhibited typical symptoms of apoptosis. In vitro cytotoxicity along with nuclear imaging confirmed EAL concentrate from soursop to be a potential drug candidate in developing new anti-cancer agent against osteosarcoma.