Aloe Emodin-Induced Apoptosis in t-HSC/Cl-6 Cells Involves a Mitochondria-Mediated Pathway

Abstract

The aim of our study was to clarify the apoptosis pathway induced by aloe emodin, an hydroxyanthraquinone present in aloe vera leaves, in rat hepatic stellate cells transformed by simian virus 40 (t-HSC/Cl-6), which retain the features of activated rat stellate cells. Apoptosis was determined by DNA fragmentation, caspase activity assay and western blotting analysis. Treatment of t-HSC/Cl-6 cells with 12.5, 25, or 50 mM aloe emodin inhibited t-HSC/Cl-6 cell viability in a dose-and time-dependent manner. The induction of apoptosis by aloe emodin was confirmed by typical DNA ladder formation and annexin v-propidium iodide flow-cytometric analysis. Aloe emodin treatment of t-HSC/Cl-6 cells caused activation of caspase-3 and caspase-9, detected with a caspase activity assay, although no change was observed in caspase-8 activity. Western blotting showed caspase-3 and caspase-9 active forms and the subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. Aloe emodin induced mitochondrial membrane depolarization. Our data also show that cytochrome c increased in the cytosol but decreased in the mitochondria in a time-dependent manner. Increased Bax and unchanged Bcl-2 levels resulted in an increased Bax/Bcl-2 ratio. Thus, our research provides evidence that aloe emodininduced apoptosis involves a mitochondria-associated apoptosis pathway.

Inhibitory effect of aloe-emodin on metastasis potential in HO-8910PM cell line

“…AE has also been reported to have antitumor activity by inducing the arrest of cell cycle in HL-60 cells 1 and apoptosis in T24 human bladder cancer cells, 2 t-HSC/Cl-6 cells, 3 and human lung non-small cell carcinoma cells. 4 However, to our knowledge, there is no available information about the effect of AE on metastasis in human carcinoma cells in vitro.…”

Anti-tumor effect of emodin on gynecological cancer cells

“…Mitochondria play a critical role in the intrinsic pathway by releasing a series of molecules, including cytochrome c. Within the cytosol, the binding of cytochrome c to adaptor protein Apaf-1 and pro-caspasse-9 molecules leads to the formation of the apoptosome that is responsible for activation of a caspase-dependent apoptotic pathway [24]. It has e.g., been reported that emodin-induced apoptosis in rat hepatic stellate cells transformed by simian virus 40 (t-HSC/ Cl-6) involves a mitochondria-mediated pathway [25].…”

Apoptosis by aloe‐emodin is mediated through down‐regulation of calpain‐2 and ubiquitin‐protein ligase E3A in human hepatoma Huh‐7 cells

“…AE has been shown to induce DNA damage through generation of ROS in human lung carcinoma cells (Lee et al, 2006). Studies have also suggested that AE could induce apoptosis via interruption of cell proliferation (Lian et al, 2005).…”