Targeting Neuroblastoma by Limonoids from the Underutilized Fruits of Xylocarpus granatum.

Abstract

Chemical examination of the chloroform extract of the underutilized fruits of Xylocarpus granatum led to the isolation and identification of limonoids (3-12) along with photogedunin C-23 epimers. These compounds were characterized by means of spectroscopic data analysis and evaluated for their antiproliferation activity against a panel of four mammalian cancer cell lines; MIAPaCa-2 (pancreatic), IMR-32 (neuroblastoma), HeLa (cervical), and MCF-7 (breast cancer) employing sulphorhodamine B assay. Among the evaluated compounds, photogedunin epimers exhibited moderate anticancer activity and inhibited the proliferation of neuroblastoma IMR-32 cells. These epimers arrested cell cycle progression in the G2/M phase and also increased the sub G1 population. Furthermore, these epimers caused reactive oxygen species production, and cleavage of poly-ADP-Ribose polymerase (PARP), the crucial marker of apoptosis. These results demonstrated the molecular mechanism behind the antiproliferative effects of photogedunin epimers derived from the underutilized fruits of Xylocarpus granatum from the mangrove forest on IMR-32 cells, indicating that these may be beneficial for the treatment of neuroblastoma.