Antiproliferative Activity, c-Myc and FGFR1 Gene Expression Profiles and Safety of Annona muricata Fruit Extract on Rhabdomyosarcoma and BALB/c Mice
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Complementary and Alternative Medical Research
Abstract
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.
Description
Keywords
Rhabdomyosarcoma, Annona muricata, c-Myc gene, FGFR1 gene, RD cell line
Citation
Chikwana, N., Maina, E. N., Gavamukulya, Y., Bulimo, W., & Wamunyokoli, F. (2021). Antiproliferative Activity, c-Myc and FGFR1 Genes Expression Profiles and Safety of Annona muricata Fruit Extract on Rhabdomyosarcoma and BALB/c Mice. Journal of Complementary and Alternative Medical Research, 14(4), 30-46. DOI: 10.9734/JOCAMR/2021/v14i430253