Tanshinone IIA inhibits the growth of pancreatic cancer BxPC‑3 cells by decreasing protein expression of TCTP, MCL‑1 and Bcl‑xL

Huang,Cheng‑Yen; Chiu,Tsung‑Lang; Kuo,Shou‑Jen; Chien,Su‑Yu; Chen,Dar‑Ren; Su,Chin‑Cheng

doi:10.3892/mmr.2013.1290

Tanshinone IIA inhibits the growth of pancreatic cancer BxPC‑3 cells by decreasing protein expression of TCTP, MCL‑1 and Bcl‑xL

Authors:
- Cheng‑Yen Huang
- Tsung‑Lang Chiu
- Shou‑Jen Kuo
- Su‑Yu Chien
- Dar‑Ren Chen
- Chin‑Cheng Su
View Affiliations

Affiliations: Department of Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C. , Tzu‑Chi University, Buddhist Tzu‑Chi General Hospital, Hualien 970, Taiwan, R.O.C., Department of Pharmacy, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
Published online on: January 25, 2013 https://doi.org/10.3892/mmr.2013.1290
Pages: 1045-1049

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

Pancreatic cancer remains a challenging disease worldwide. Tanshinone IIA (Tan‑IIA) is one of the active constituents of Danshen (Radix Salviae miltiorrhizae). Tan‑IIA has been hypothesized to inhibit numerous human cancer cells by various molecular mechanisms. However, the efficacy and molecular mechanism of Tan‑IIA action in pancreatic cancer has not been well studied. In the present study, the cytotoxicity of Tan‑IIA in human pancreatic cancer BxPC‑3 cells was evaluated by MTT assay. Cell cycle analysis of BxPC‑3 cells treated with Tan‑IIA was performed by flow cytometry (FACS). Protein expression levels of TCTP, Mcl‑1, Bcl‑xL, Bax and Caspase‑3 in BxPC‑3 cells were measured by western blot analysis. The results revealed that Tan‑IIA inhibited BxPC‑3 cells in a time‑ and dose‑dependent manner. FACS analysis demonstrated that Tan‑IIA increases the rate of sub‑G1 phase. BxPC‑3 cells treated with Tan‑IIA were identified to upregulate protein expression of Bax and Caspase‑3 and downregulate expression of TCTP, Mcl‑1 and Bcl‑xL. These results indicate that Tan‑IIA may inhibit BxPC‑3 human pancreatic cancer cells through the induction of apoptosis by decreasing protein expression of TCTP, Mcl‑1 and Bcl‑xL and increasing Bax expression in vitro. The chemotherapeutic potential of Tan‑IIA for human pancreatic cancer warrants further study.

View Figures

View References

1	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
3	Verhoef MJ, Balneaves LG, Boon HS and Vroegindewey A: Reasons for and characteristics associated with complementary and alternative medicine use among adult cancer patients: a systematic review. Integr Cancer Ther. 4:274–286. 2005. View Article : Google Scholar : PubMed/NCBI
4	Che AJ, Zhang JY, Li CH, Chen XF, Hu ZD and Chen XG: Separation and determination of active components in Radix Salviae miltiorrhizae and its medicinal preparations by nonaqueous capillary electrophoresis. J Sep Sci. 27:569–575. 2004.PubMed/NCBI
5	Zhou L, Zuo Z and Chow MS: Danshen: an overview of its chemistry, pharmacology, pharmacokinetics and clinical use. J Clin Pharmacol. 45:1345–1359. 2005. View Article : Google Scholar : PubMed/NCBI
6	Su CC and Lin YH: Tanshinone IIA downregulates the protein expression of ErbB-2 and upregulates TNF-α in colon cancer cells in vitro and in vivo. Int J Mol Med. 22:847–851. 2008.PubMed/NCBI
7	Su CC and Lin YH: Tanshinone IIA inhibits human breast cancer cells through increased Bax to Bcl-xL ratios. Int J Mol Med. 22:357–361. 2008.PubMed/NCBI
8	Chiu TL and Su CC: Tanshinone IIA induces apoptosis in human lung cancer A549 cells through the induction of reactive oxygen species and decreasing the mitochondrial membrane potential. Int J Mol Med. 25:231–236. 2010.PubMed/NCBI
9	Cheng CY and Su CC: Tanshinone IIA may inhibit the growth of small cell lung cancer H146 cells by up-regulating the Bax/Bcl-2 ratio and decreasing mitochondrial membrane potential. Mol Med Rep. 3:645–650. 2010.PubMed/NCBI
10	Cheng CY and Su CC: Tanshinone IIA inhibits Hep-J5 cells by increasing calreticulin, Caspase-12 and GADD153 protein expression. Int J Mol Med. 26:379–385. 2010.PubMed/NCBI
11	Fronza M, Murillo R, Œlusarczyk S, et al: In vitro cytotoxic activity of abietane diterpenes from Peltodon longipes as well as Salvia miltiorrhiza and Salvia sahendica. Bioorg Med Chem. 19:4876–4881. 2011. View Article : Google Scholar : PubMed/NCBI
12	Chitpatima ST, Makrides S, Bandyopadhyay R and Brawerman G: Nucleotide sequence of a major messenger RNA for a 21 kilodalton polypeptide that is under translational control in mouse tumor cells. Nucleic Acids Res. 16:23501988. View Article : Google Scholar : PubMed/NCBI
13	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
14	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
15	Li F, Zhang D and Fujise K: Characterization of fortilin, a novel antiapoptotic protein. J Biol Chem. 276:47542–47549. 2001. View Article : Google Scholar : PubMed/NCBI
16	Zhang D, Li F, Weidner D, Mnjoyan ZH and Fujise K: Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and Fortilin. The potential role of MCL1 as a fortilin chaperone. J Biol Chem. 277:37430–37438. 2002. View Article : Google Scholar : PubMed/NCBI
17	Tuynder M, Susini L, Prieur S, et al: Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci USA. 99:14976–14981. 2002. View Article : Google Scholar : PubMed/NCBI
18	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
19	Liu H, Peng HW, Cheng YS, Yuan HS and Yang-Yen HF: 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
20	Yang Y, Yang F, Xiong Z, et al: An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity. Oncogene. 24:4778–4788. 2005. View Article : Google Scholar : PubMed/NCBI
21	Susini L, Besse S, Duflaut D, et al: CTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ. 15:1211–1220. 2008. View Article : Google Scholar : PubMed/NCBI
22	Won SH, Lee HJ, Jeong SJ, et al: Tanshinone IIA induces mitochondria dependent apoptosis in prostate cancer cells in association with an inhibition of phosphoinositide 3-kinase/AKT pathway. Biol Pharm Bull. 33:1828–1834. 2010. View Article : Google Scholar : PubMed/NCBI