Methanolic Extract of Mallotus roxburghianus Muell. Exhibit Anti-Cancer Activity against Dalton’s Lymphoma Ascites (DLA) bearing Mice via Alterations of Apoptotic Genes E xpression and Redox-Homeostasis

Abstract

Objectives:The current study examined the anti-cancer effects of methanolic extract of Mallotus roxburghianus (MRME) using Dalton's Lymphoma Ascites (DLA) bearing mice. Methods: According to OECD guidelines, the acute toxicity of MRME was assessed, and the LD 50 of MRME was estimated using probit analysis. The effects of MRME on survival time, weight change, and antioxidant/oxidant status were determined in DLA mice by administering the animals with different doses of MRME, and doxorubicin was used as a standard reference drug. Cytotoxicity, activities of serum enzymes, and haematological parameters were also determined after treatment with MRME. Effects of MRME on DNA damage and the differential gene expression of apoptotic genes were also studied using Comet assay and qPCR techniques respectively. Findings: MRME significantly reduced tumour growth and extended the survival duration of tumour-bearing mice with increased in MST (26.0 ± 0.72), AST (23.0 ± 0.60), % IMLS (79.3 ± 0.58) and % IALS (50.0 ± 0.91) after treatment with 150 mg/kg. MRME also decreased antioxidant activities and enhanced lipid peroxidation. Decreased RBC levels and haemoglobin content in DLA mice were significantly reversed by MRME treatment. MRME also reduces AST, ALT, LDH, and CRE levels, which were otherwise increased in the DLA control animals. The apoptosis-based anti-cancer effects of M. roxburghianus were revealed by the induction of DNA damage, up-regulation of pro-apoptotic genes, and down-regulation of anti-apoptotic genes in DLA mice after M. roxburghianus treatment. MRME treatment increased the relative expressions of pro-apoptotic genes such as Apaf1, p53 and Bax by 3.19, 3.81 and https://www.indjst.org/