Antiproliferative Activity and Apoptotic Efficiency of Syzygium cumini Bark Methanolic Extract against EAC Cells In Vivo.

ABSTRACT

BACKGROUND: Syzygium cumini is one of the evidence-based traditional medicinal plant used in the treatment of various ailments. OBJECTIVES: Herein, the antioxidant property and anticancer property of Syzygium cumini against Ehrlich Ascites Carcinoma (EAC) cells were examined to find effective chemotherapeutics. METHODS: In vitro assays, and phytochemical and chromatographic analyses were used to determine antioxidant properties and chemical constituents of Syzygium cummini Bark Methanolic Extract (SCBME). Functional assays were used to measure the anticancer activity of SCBME. Fluorescence microscopy and RT-PCR were used to examine morphological and molecular changes of EAC cells followed by SCBME treatment. RESULTS: Phytochemical and GC-MS analyses confirmed the presence of compounds with antioxidant and anticancer activities. Accordingly, we have noted a strong antioxidant activity of SCBME with an IC50 value of ~10µg/ml. Importantly, SCBME exerted a dose-dependent anticancer activity with significant inhibition of EAC cell growth (71.08±3.53%; p<0.001), reduction of tumor burden (69.50%; p<0.01) and increase of life span (73.13%; p<0.001) of EAC-bearing mice at 75mg/kg/day. Besides, SCBME restored the blood toxicity towards normal in EAC-bearing mice (p<0.05). DISCUSSION: SCBME treated EAC cells showed apoptotic features under a fluorescence microscope and fragmented DNA in DNA laddering assay. Moreover, up-regulation of the tumor suppressor p53 and pro-apoptotic Bax and down-regulation of NF-κB and anti-apoptotic Bcl-2 genes implied induction of apoptosis followed by SCBME treatment. CONCLUSION: The antiproliferative activity of SCBME against EAC cells is likely due to apoptosis, mediated by regulation of p53 and NF-κB signaling. Thus, SCBME can be considered as a useful resource in cancer chemotherapy.