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

Liu,Jin-Xiang; Zhang,Jian-Hong; Li,Hong-Hai; Lai,Fu-Ji; Chen,Kang-Jie; Chen,Hui; Luo,Jiang; Guo,Hong-Chun; Wang,Zhao-Hong; Lin,Sheng-Zhang

doi:10.3892/or.2012.2042

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

Authors:
- Jin-Xiang Liu
- Jian-Hong Zhang
- Hong-Hai Li
- Fu-Ji Lai
- Kang-Jie Chen
- Hui Chen
- Jiang Luo
- Hong-Chun Guo
- Zhao-Hong Wang
- Sheng-Zhang Lin
View Affiliations

Affiliations: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College,Wenzhou 325027, P.R. China, Department of Hepatobiliary-Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou 310003, P.R. China
Published online on: September 18, 2012 https://doi.org/10.3892/or.2012.2042
Pages: 1991-1996

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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), E10 group (emodin 10 mg/kg), E20 group (emodin 20 mg/kg), E40 group (emodin 40 mg/kg) and E80 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 E40 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.

View Figures

View References

1	Maisonneuve P and Lowenfels AB: Epidemiology of pancreatic cancer: an update. Dig Dis. 28:645–656. 2010. View Article : Google Scholar : PubMed/NCBI
2	Triano LR, Chang BW and Saif MW: New developments in the treatment of locally advanced pancreatic cancer. In: Highlights from the 45th ASCO annual meeting; Orlando, FL JOP. 10. pp. 366–372. 2009, PubMed/NCBI
3	Conroy T, Desseigne F, Ychou M, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 364:1817–1825. 2011. View Article : Google Scholar : PubMed/NCBI
4	Yu CX, Zhang XQ, Kang LD, et al: Emodin induces apoptosis in human prostate cancer cell LNCaP. Asian J Androl. 10:625–634. 2008. View Article : Google Scholar : PubMed/NCBI
5	Damodharan U, Ganesan R and Radhakrishnan UC: Expression of MMP2 and MMP9 (gelatinases A and B) in human colon cancer cells. Appl Biochem Biotechnol. 165:1245–1252. 2011. View Article : Google Scholar : PubMed/NCBI
6	Guo HC, Bu HQ, Luo J, et al: Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic cancer xenograft model in vivo via inhibition of inhibitors of apoptosis. Int J Oncol. 40:1849–1857. 2012.PubMed/NCBI
7	Baumann S, Fas SC, Giaisi M, et al: Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca²⁺-dependent apoptosis. Blood. 111:2354–2363. 2008. View Article : Google Scholar : PubMed/NCBI
8	Li S, Zhang B, Jiang D, Wei Y and Zhang N: Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae. BMC Bioinformatics. 11:S62010. View Article : Google Scholar : PubMed/NCBI
9	Oh B, Hu G, Kao S, Gebski V, Walls R, Truong L, Beale P and Clarke S: The safety and tolerability of Chinese herbal medicine in cancer patients receiving chemotherapy: pilot study. WebmedCentral Chinese Medicine. 2:WMC0016712011.
10	Yim H, Lee YH, Lee CH and Lee SK: Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor. Planta Med. 65:9–13. 1999. View Article : Google Scholar
11	Wang L, Lin L and Ye B: Electrochemical studies of the interaction of the anticancer herbal drug emodin with DNA. J Pharm Biomed Anal. 42:625–629. 2006. View Article : Google Scholar : PubMed/NCBI
12	Liu A, Chen H, Tong H, et al: Emodin potentiates the antitumor effects of gemcitabine in pancreatic cancer cells via inhibition of nuclear factor-kappaB. Mol Med Rep. 4:221–227. 2011.PubMed/NCBI
13	Chen H, Wei W, Guo Y, et al: Enhanced effect of gemcitabine by emodin against pancreatic cancer in vivo via cytochrome C-regulated apoptosis. Oncol Rep. 25:1253–1261. 2011.PubMed/NCBI
14	Fulda S, Galluzzi L and Kroemer G: Targeting mitochondria for cancer therapy. Nat Rev Drug Discov. 9:447–464. 2010. View Article : Google Scholar
15	Leber B, Lin J and Andrews DW: Still embedded together binding to membranes regulates Bcl-2 protein interactions. Oncogene. 29:5221–5230. 2010. View Article : Google Scholar : PubMed/NCBI
16	Yang CL, Ma YG, Xue YX, Liu YY, Xie H and Qiu GR: Curcumin induces small cell lung cancer NCI-H446 cell apoptosis via the reactive oxygen species-mediated mitochondrial pathway and not the cell death receptor pathway. DNA Cell Biol. 31:139–150. 2012. View Article : Google Scholar : PubMed/NCBI
17	Ly JD, Grubb DR and Lawen A: The mitochondrial membrane potential (deltapsi(m)) in apoptosis: an update. Apoptosis. 8:115–128. 2003. View Article : Google Scholar : PubMed/NCBI
18	Tian X, Luo Y, Liu YP, et al: Downregulation of Bcl-2 and survivin expression and release of Smac/DIABLO involved in bufalin-induced HL-60 cell apoptosis. Zhonghua Xue Ye Xue Za Zhi. 27:21–24. 2006.(In Chinese).
19	Halestrap AP: Calcium, mitochondria and reperfusion injury: a pore way to die. Biochem Soc Trans. 34:232–237. 2006. View Article : Google Scholar : PubMed/NCBI
20	Lopez M, Welsh K, Yuan H, et al: Antagonists of IAP-family anti-apoptotic proteins BTI. Probe Reports from the NIH Molecular Libraries Program. 2010
21	Kim MP and Gallick GE: Gemcitabine resistance in pancreatic cancer: picking the key players. Clin Cancer Res. 14:1284–1285. 2008. View Article : Google Scholar : PubMed/NCBI
22	Long J, Zhang Y, Yu X, et al: Overcoming drug resistance in pancreatic cancer. Expert Opin Ther Targets. 15:817–828. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tan W, Lu J, Huang M, et al: Anti-cancer natural products isolated from Chinese medicinal herbs. Chin Med. 6:272011. View Article : Google Scholar : PubMed/NCBI
24	Wei WT, Chen H, Ni ZL, et al: Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation. Int J Oncol. 39:1381–1390. 2011.PubMed/NCBI
25	Wang QJ, Cai XB, Liu MH, Hu H, Tan XJ and Jing XB: Apoptosis induced by emodin is associated with alterations of intracellular acidification and reactive oxygen species in EC-109 cells. Biochem Cell Biol. 88:767–774. 2010. View Article : Google Scholar : PubMed/NCBI
26	Wang W, Sun Y, Li X, et al: Emodin potentiates the anticancer effect of cisplatin on gallbladder cancer cells through the generation of reactive oxygen species and the inhibition of survivin expression. Oncol Rep. 26:1143–1148. 2011.PubMed/NCBI