Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI‐3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo

Abstract

Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ΔΨm by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

Involvement of PPARγ in emodin-induced HK-2 cell apoptosis

“…In the present study, we demonstrated that the levels of cleaved caspase 3 fragments were elevated in emodin-treated HK-2 cells, which is consistent with previous studies (Wang et al, 2008(Wang et al, , 2007. These data suggested that caspase 3 plays a key role in emodin-induced apoptosis in HK-2 cells, even though caspase-independent pathway is involved in emodin-induced apoptosis in mice leukemia WEHI-3 cells (Chang et al, 2011). Caspase 3 is a critical and common executioner protease in apoptosis, and can be activated via two main signaling pathways: the death receptor-mediated extrinsic pathway and the mitochondria-mediated intrinsic pathway (Ashkenazi and Dixit, 1998;Green and Reed, 1998).…”

Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice

“…The dose of particle (20 g/mouse) we used here has been selected from our previous study (Nemmar et al, 2009a) and is comparable to the doses employed in previous animal models of particulate air pollution exposure (Kido et al, 2011;Mutlu et al, 2007;Nemmar et al, 2011a). Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from many herbs, is known to inhibit the production of inflammatory cytokines such as TNF␣, IL-6 and IL1␤ (Li et al, 2013;Xiao et al, 2014) and to have strong antioxidant and antiapoptotic actions Chang et al, 2011). In the present study, we elected to test emodin against DEP-induced lung toxicity, as the latter is associated with oxidative stress and inflammation (Nemmar et al, 2009a(Nemmar et al, , 2011a(Nemmar et al, , 2012b.…”

“…Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from the Chinese herb Radix et Rhizoma Rhei, has been shown to have strong anticancer (Chang et al, 2011) http://dx.doi.org/10.1016/j.resp.2015.05.006 1569-9048/© 2015 Elsevier B.V. All rights reserved. and antioxidant activities Waly et al, 2013).…”

Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer

“…With overproduction of H 2 O 2 , concentration of both these enzymes decreases considerably, indicating that emodin induces apoptosis via the mitochondrial pathway [112]. Chang et al [113] showed that treatment with emodin can enhance phagocytic activity by monocytes and macrophages in the WEHI-3 leukemia murine model and also reduce liver and spleen weights. The potential of emodin to inhibit proliferation of K562 cell growth in vivo was shown by concomitant decrease in tumor volume and weight of xenografted tumor in nude mice.…”