Antiproliferative Activity, c-Myc and FGFR1 Genes Expression Profiles and Safety of Annona muricata Fruit Extract on Rhabdomyosarcoma and BALB/c Mice

Abstract

Introduction: Rhabdomyosarcoma is an aggressive solid tumour of skeletal muscles origin whose current treatment is associated with high expenses, severe side effects, drug resistance and tumour regrowth. There is a need to develop safer and more effective chemotherapeutic agents. Annona muricata is one of the widely used plants in treating various diseases due to its reported effectiveness. However, there is a dearth of scientific information regarding the efficacy of Annona muricata on rhabdomyosarcoma and its safety. This study aimed to evaluate the effects of Annona muricata ethanolic fruit extract on the antiproliferative activity and gene expression in RD cell line, including its biosafety in BALB/c mice. Materials and Methods: The resazurin metabolic assay was used to assess the antiproliferative and cytotoxic activities of Annona muricata ethanolic fruit extract on RD and Vero cells. Quantitative real-time polymerase chain reaction was used to assess the gene expression profiles on c-Myc and FGFR1 genes. To evaluate the safety of the Annona muricata ethanolic fruit extract, an acute oral toxicity study was conducted on BALB/c mice. Results: Annona muricata ethanolic fruit extract significantly inhibited the growth of RD cells in a concentration and time-dependent manner while being highly selective on the Vero cells (selectivity index of 6.10 at 72h) compared to a reference cancer drug, doxorubicin (Selectivity index of 1.38 at 72hr). The c-Myc and FGFR1 genes were under expressed in RD cells treated with Annona muricata ethanolic fruit extract with (3.4 and 6.1 fold), respectively, compared to untreated cells. Acute oral toxicity studies revealed no significant difference (p ≥ 0.05) between the treated mice and the control group, indicating the safety of the fruit extract. Conclusion: Annona muricata ethanolic fruit extract can serve as effective and safe anticancer agents against rhabdomyosarcoma and further develop into standard drugs. Non-human primate studies need to be undertaken to step towards the clinical utilization of the Annona muricata ethanolic fruit extract in the management of rhabdomyosarcoma.