Emodin induces Panc-1 cell apoptosis via declining the mitochondrial membrane potential

Abstract

Abstract. In this study, we investigated the apoptotic effect of emodin on human pancreatic cancer cell line Panc-1 in vitro and in vivo as well as the possible mechanisms involved. In vitro, human pancreatic cancer cell line Panc-1 was exposed to varying concentrations of emodin (0,10,20, 40 or 80 µmol/l). Then the mitochondrial membrane potential (MMP) was analyzed by JC-1 staining, cell apoptosis was analyzed by flow cytometry (FCM) and cell proliferation was analyzed by MTT. In vivo, nude mice orthotopically implanted were randomly divided into five groups to receive treatments by different doses of emodin: control group (normal saline 0.2 ml), E 10 group (emodin 10 mg/kg), E 20 group (emodin 20 mg/kg), E 40 group (emodin 40 mg/kg) and E 80 group (emodin 80 mg/kg). Each mouse was treated 5 times by intraperitoneal injection of emodin every 3 days. During the treatment, the feeding stuff was recorded. One week after the last treatment, we recorded the body weight and the maximum diameter of tumor in each group before the mice were sacrificed. Then the cell apoptosis of the tumor was tested by TUNEL assay. The results in vitro showed that the MMP of the cells declined and the apoptosis rate increased with the emodin concentration increasing and the cell proliferation of each group was inhibited in a dose-and time-dependent manner by emodin. The feeding stuff curve did not decline significantly in E 40 group and the apoptosis rate of the tumor cells in this group was higher than the lower-dose groups. Taken together, our results demonstrate that emodin may induce the pancreatic cancer cell apoptosis via declining the MMP and a moderate dose of emodin improved the living state of the model mice.

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

“…The molecular mechanisms underlying emodin-induced apoptosis are different depending on the cell types (Liu et al, 2012;Yu et al, 2013). 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.…”

Emodin inhibits angiogenesis in pancreatic cancer by regulating the transforming growth factor-β/drosophila mothers against decapentaplegic pathway and angiogenesis-associated microRNAs

“…These results revealed that emodin inhibits the growth of pancreatic cancer through a variety of different mechanisms (15), suggesting emodin as a promising natural drug for the treatment of pancreatic cancer.…”

“…The mice in the control group were each injected with 0.2 ml 0.9% sodium chloride (Shanghai Chemical Reagent Plant, Shanghai,China) into the abdominal cavity. The mice in the E20, E40 and E80 groups were injected with 20, 40 and 80 mg/kg emodin, respectively, using the same method as the control (15). Each group was treated three times each week for 2 weeks.…”

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

“…Similarly, an emodin azide methyl anthraquinone derivative (AMAD) induced apoptosis via mitochondrial pathway involving caspase-8 activation in both human breast cancer cell line MDA-MB-453 and human lung adenocarcinoma Calu-3 cells [85]. Liu et al [87] reported that emodin induced apoptosis in human pancreatic cancer cell line Panc-1 by declining the mitochondrial membrane potential (MMP) in a dose-and time-dependent manner.…”

“…Moreover, emodin could also induce apoptosis by mitochondria-dependent activation of caspase-3 and -9 and by up-regulating expression of Bax protein and down-regulating Bcl-2 protein expression [114]. Liu et al [87] showed that emodin, given i.p. to orthotopically implanted nude mice at doses of 0, 10, 20, 40, 80 mg/kg, 5 times every 3 days, induced the pancreatic cancer cell apoptosis via declining the mitochondrial membrane potential in a dose-dependent manner.…”