Apoptosis of Dalton's lymphoma due to in vivo treatment with emodin is associated with modulations of hydrogen peroxide metabolizing antioxidant enzymes.

Abstract

The evolving concept of pro-oxidative mechanism-based antitumor activity of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), derived mainly from in vitro studies, needs to be defined for in vivo tumor models. The present article describes apoptosis and regression of Dalton's lymphoma (DL) in mice by emodin vis a vis modulations of hydrogen peroxide (H2O2) metabolizing antioxidant enzymes in the tumor cells in vivo. A non-toxic dose (40 mg/kg bw) of emodin, given intraperitoneally to the DL bearing mice daily up to 12th post DL transplantation day, caused a significant decline (P < 0.05) in the number of viable DL cells and could significantly increase life span of the DL mice (P < 0.01). A significant decline in Bcl2/Bax ratio consistent with the release of mitochondrial cytochrome c release in DL cells from emodin-treated DL mice suggested that emodin could induce mitochondrial pathway of apoptosis in the DL cells in vivo. Apoptosis of DL cells by emodin was further confirmed by the appearance of smaller DNA fragments on DNA ladder analysis. Over activation of both, the Cu-Zn-superoxide dismutases (SOD1) and Mn-SOD (SOD2), has been found correlated with the tumor suppression. Emodin caused significant increases in the expression and activity of SOD1 and SOD2 in the DL cells. H2O2 produced by SODs is degraded by catalase and glutathione peroxidase in the cells. Both these enzymes were observed to be declined significantly with a concomitant increment in H2O2 concentration (P < 0.01) in the DL cells from emodin-treated DL mice. It is concluded that emodin is able to induce mitochondrial pathway of apoptosis in the DL cells in vivo via reciprocal modulations of H2O2 producing and degrading antioxidant enzymes.

• Authors: Krishna Beer Singh, Surendra Kumar Trigun
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 67 Issue 2 Pg. 439-49 (Nov 2013) ISSN: 1559-0283 [Electronic] United States
• PMID: 22038303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Hydrogen Peroxide
• Emodin

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology)
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Emodin (adverse effects, pharmacology)
• Hydrogen Peroxide (metabolism)
• Liver (drug effects, metabolism)
• Longevity (drug effects)
• Lymphoma, T-Cell (enzymology, metabolism, pathology)
• Mice