Sann-Joong-Kuey-Jian-Tang decreases the protein expression of Mcl‑1 and TCTP and increases that of TNF-α and Bax in BxPC‑3 pancreatic carcinoma cells

Chien,Su-Yu; Kuo,Shou-Jen; Chen,Dar-Ren; Su,Chin-Cheng

doi:10.3892/ijmm.2013.1369

Sann-Joong-Kuey-Jian-Tang decreases the protein expression of Mcl‑1 and TCTP and increases that of TNF-α and Bax in BxPC‑3 pancreatic carcinoma cells

Authors:
- Su-Yu Chien
- Shou-Jen Kuo
- Dar-Ren Chen
- Chin-Cheng Su
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Affiliations: Department of Pharmacy, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C., Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
Published online on: May 8, 2013 https://doi.org/10.3892/ijmm.2013.1369
Pages: 85-92

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Abstract

Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicinal prescription, has been used for the treatment of lymphadenopathy and solid tumors, and has shown therapeutic potential in several human malignant tumor cell lines. However, the efficacy and molecular mechanisms of action of SJKJT in human pancreatic cancer have not yet been elucidated. In the present study, we evaluated the cytotoxic effects of SJKJT on BxPC-3 human pancreatic carcinoma cells by MTT assay. The protein expression levels of myeloid cell leukemia 1 protein (Mcl-1), translationally controlled tumor protein (TCTP), tumor necrosis factor-α (TNF‑α), caspase-8, caspase-3, Bax and Bcl-2 family in the BxPC-3 cells were measured by western blot analysis. The cell cycle was analyzed by flow cytometry. The protein expression of caspase-3 was also detected by immunocytochemistry (ICC). The results revealed that SJKJT inhibited the proliferation of BxPC-3 cells in a time- and dose-dependent manner. The protein expression levels of TNF-α, caspase-8, caspase-3 and Bax increased in the BxPC-3 cells treated with SJKJT; however, the levels of Mcl-1, TCTP and Bcl-xL decreased. The results also demonstrated that SJKJT increased the percentage of BxPC-3 cells in the sub-G1 phase. In addition, ICC staining indicated that the protein expression of caspase-3 was upregulated in the BxPC-3 cells treated with SJKJT. These findings indicate that SJKJT inhibits the proliferation of BxPC-3 cells through the extrinsic and intrinsic pathway, inducing apoptosis in vitro. Our study, using BxPC-3 human pancreatic cancer cells, demonstrates that SJKJT has potential as a chemotherapeutic agent for the treatment of pancreatic cancer. Further sutdies are warranted to fully elucidate its mechanisms of action.

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1.	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
2.	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
3.	Louvet C, Labianca R, Hammel P, et al: Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 23:3509–3516. 2005. View Article : Google Scholar : PubMed/NCBI
4.	Heinemann V, Quietzsch D, Gieseler F, et al: Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 24:3946–3952. 2006. View Article : Google Scholar : PubMed/NCBI
5.	Herrmann R, Bodoky G, Ruhstaller T, et al: Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 25:2212–2217. 2007. View Article : Google Scholar
6.	Burris HA III, Moore MJ, Andersen J, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 15:2403–2413. 1997.PubMed/NCBI
7.	Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D and Sarkar FH: Pancreatic cancer: understanding and overcoming chemoresistance. Nat Rev Gastroenterol Hepatol. 8:27–33. 2011. View Article : Google Scholar : PubMed/NCBI
8.	Hsu YL, Yen MH, Kuo PL, et al: San-Zhong-Kui-Jian-Tang, a traditional Chinese medicine prescription, inhibits the proliferation of human breast cancer cells by blocking cell cycle progression and inducing apoptosis. Biol Pharm Bull. 29:2388–2394. 2006. View Article : Google Scholar
9.	Yang CH and Craise LM: Development of human epithelial cell systems for radiation risk assessment. Adv Space Res. 14:115–120. 1994. View Article : Google Scholar : PubMed/NCBI
10.	Cheng CY, Lin YH and Su CC: Sann-Joong-Kuey-Jian-Tang increases the protein expression of microtubule-associated protein II light chain 3 in human colon cancer colo 205 cells. Mol Med Rep. 2:707–711. 2009.PubMed/NCBI
11.	Cheng CY, Lin YH and Su CC: Sann-Joong-Kuey-Jian-Tang up-regulates the protein expression of Fas and TNF-α in colo 205 cells in vivo and in vitro. Mol Med Rep. 3:63–67. 2010.PubMed/NCBI
12.	Chen YL, Yan MY, Chien SY, Kuo SJ, Chen DR, Cheng CY and Su CC: Sann-Joong-Kuey-Jian-Tang inhibits hepatocellular carcinoma Hep-G2 cell proliferation by increasing TNF-α, Caspase-8, Caspase- 3 and Bax but by decreasing TCTP and Mcl-1 expression in vitro. Mol Med Rep. 7:1487–1493. 2013.PubMed/NCBI
13.	Carswell EA, Old LJ, Kassel RL, et al: An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 72:3666–3670. 1975. View Article : Google Scholar : PubMed/NCBI
14.	Gaur U and Aggarwal BB: Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol. 66:1403–1408. 2003. View Article : Google Scholar : PubMed/NCBI
15.	Yenofsky R, Cereghini S, Krowczynska A and Brawerman G: Regulation of mRNA utilization in mouse erythroleukemia cells induced to differentiate by exposure to dimethyl sulfoxide. Mol Cell Biol. 3:1197–1203. 1983.PubMed/NCBI
16.	Chitpatima ST, Makrides S, Bandyopadhyay R and Brawerman G: Nucleotide sequence of a major messenger RNA for a 21 kilo-dalton polypeptide that is under translational control in mouse tumor cells. Nucleic Acids Res. 16:23501988. View Article : Google Scholar
17.	Bommer UA, Lazaris-Karatzas A, De Benedetti A, et al: Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E. Cell Mol Biol Res. 40:633–641. 1994.PubMed/NCBI
18.	Bommer UA and Thiele BJ: The translationally controlled tumour protein (TCTP). Int J Biochem Cell Biol. 36:379–385. 2004. View Article : Google Scholar
19.	Zhang D, Li F, Weidner D, et al: Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and Fortilin. The potential role of MCL-1 as a fortilin chaperone. J Biol Chem. 277:37430–37438. 2002. View Article : Google Scholar : PubMed/NCBI
20.	Graidist P, Phongdara A and Fujise K: Antiapoptotic protein partners fortilin and MCL1 independently protect cells from 5-fluorouracil-induced cytotoxicity. J Biol Chem. 279:40868–40875. 2004. View Article : Google Scholar : PubMed/NCBI
21.	Liu H, Peng HW, Cheng YS, et al: Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Mol Cell Biol. 25:3117–3126. 2005. View Article : Google Scholar : PubMed/NCBI
22.	Susini L, Besse S, Duflaut D, et al: TCTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ. 15:1211–1220. 2008. View Article : Google Scholar : PubMed/NCBI