Synergistic effects of baicalein with gemcitabine or docetaxel on the proliferation, migration and apoptosis of pancreatic cancer cells

Liu,Pan; Feng,Jiarui; Sun,Meng; Yuan,Wen; Xiao,Ruijing; Xiong,Jie; Huang,Xiaoxin; Xiong,Meng; Chen,Wu; Yu,Xin; Sun,Qian; Zhao,Xiaojie; Zhang,Qiuping; Shao,Liang

doi:10.3892/ijo.2017.4153

Synergistic effects of baicalein with gemcitabine or docetaxel on the proliferation, migration and apoptosis of pancreatic cancer cells

Authors:
- Pan Liu
- Jiarui Feng
- Meng Sun
- Wen Yuan
- Ruijing Xiao
- Jie Xiong
- Xiaoxin Huang
- Meng Xiong
- Wu Chen
- Xin Yu
- Qian Sun
- Xiaojie Zhao
- Qiuping Zhang
- Liang Shao
View Affiliations

Affiliations: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Immunology, Basic School, Wuhan University, Wuhan, Hubei 430072, P.R. China, Department of Blood Transfusion, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Basic School, Wuhan University, Wuhan, Hubei 430072, P.R. China
Published online on: October 11, 2017 https://doi.org/10.3892/ijo.2017.4153
Pages: 1878-1886

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

Baicalein, a type of flavonoids extracted from Scutellaria baicalensis Georgi, has been reported to be a very promising drug for pancreatic cancer. However, it is unclear whether combination of baicalein with gemcitabine or docetaxel is synergistic to the treatment for pancreatic cancer (PC). We investigated the combinational effects of baicalein with gemcitabine or docetaxel on proliferation, cell cycle, migration and apoptosis of human PC cells. Administration of baicalein alone significantly inhibit the proliferation of PC cells. Notably, when it is combined with gemcitabine or docetaxel, combination index (CI) values calculated by Calcusyn software are smaller than 1, indicating the synergism of baicalein with gemcitabine or docetaxel for the treatment of PC cells. Consistently, EdU assay showed that administration of baicalein significantly enhanced the capacity of gemicitabine to inhibit proliferation of PC cells. Cell cycle analysis showed that high-concentration of baicalein was able to arrest PC cells in the S phase. Furthermore, low concentration of baicalein in combination with either gemcitabine or docetaxel exhibited strong suppression on the migration of PC cells. A further study using transmission electron microscope (TEM), DAPI staining and western blot showed that baicalein induced-apoptosis of PC cells might be via caspase-3/PARP signaling pathway. Notably, combination treatment was able to induce more severe cell apoptosis of PC cells. In conclusion, baicalein exhibited synergistic effects with gemcitabine or docetaxel on the treatment of PC cells.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Hidalgo M: Pancreatic cancer. N Engl J Med. 362:1605–1617. 2010. View Article : Google Scholar : PubMed/NCBI
3	Humphris JL, Johns AL, Simpson SH, Cowley MJ, Pajic M, Chang DK, Nagrial AM, Chin VT, Chantrill LA, Pinese M, et al Australian Pancreatic Cancer Genome Initiative: Clinical and pathologic features of familial pancreatic cancer. Cancer. 120:3669–3675. 2014. View Article : Google Scholar : PubMed/NCBI
4	Hidalgo M: New insights into pancreatic cancer biology. Ann Oncol. 23(Suppl 10): x135–x138. 2012. View Article : Google Scholar : PubMed/NCBI
5	Garrido-Laguna I and Hidalgo M: Pancreatic cancer: From state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol. 12:319–334. 2015. View Article : Google Scholar : PubMed/NCBI
6	Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 369:1691–1703. 2013. View Article : Google Scholar : PubMed/NCBI
7	Yassine F, Salibi E and Gali-Muhtasib H: Overview of the formulations and analogs in the taxanes' story. Curr Med Chem. 23:4540–4558. 2016. View Article : Google Scholar : PubMed/NCBI
8	Mantripragada KC and Safran H: Optimizing initial chemotherapy for metastatic pancreatic cancer. Future Oncol. 12:1125–1133. 2016. View Article : Google Scholar : PubMed/NCBI
9	Liu H, Dong Y, Gao Y, Du Z, Wang Y, Cheng P, Chen A and Huang H: The fascinating effects of baicalein on cancer: A review. Int J Mol Sci. 17:172016. View Article : Google Scholar
10	Donald G, Hertzer K and Eibl G: Baicalein - an intriguing therapeutic phytochemical in pancreatic cancer. Curr Drug Targets. 13:1772–1776. 2012. View Article : Google Scholar : PubMed/NCBI
11	Wu JY, Tsai KW, Li YZ, Chang YS, Lai YC, Laio YH, Wu JD and Liu YW: Anti-bladder-tumor effect of baicalein from Scutellaria baicalensis Georgi and its application in vivo. Evid Based Complement Alternat Med. 2013:5797512013.PubMed/NCBI
12	Taniguchi H, Yoshida T, Horinaka M, Yasuda T, Goda AE, Konishi M, Wakada M, Kataoka K, Yoshikawa T and Sakai T: Baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance via two different cell-specific pathways in cancer cells but not in normal cells. Cancer Res. 68:8918–8927. 2008. View Article : Google Scholar : PubMed/NCBI
13	Wang L, Ling Y, Chen Y, Li CL, Feng F, You QD, Lu N and Guo QL: Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. Cancer Lett. 297:42–48. 2010. View Article : Google Scholar : PubMed/NCBI
14	Wang CZ, Zhang CF, Chen L, Anderson S, Lu F and Yuan CS: Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin. Int J Oncol. 47:1749–1758. 2015.PubMed/NCBI
15	Li-Weber M: New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 35:57–68. 2009. View Article : Google Scholar
16	Lu QY, Zhang L, Moro A, Chen MC, Harris DM, Eibl G and Go VL: Detection of baicalin metabolites baicalein and oroxylina in mouse pancreas and pancreatic xenografts. Pancreas. 41:571–576. 2012. View Article : Google Scholar :
17	Takahashi H, Chen MC, Pham H, Angst E, King JC, Park J, Brovman EY, Ishiguro H, Harris DM, Reber HA, et al: Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochim Biophys Acta. 1813:1465–1474. 2011. View Article : Google Scholar : PubMed/NCBI
18	Caparello C, Meijer LL, Garajova I, Falcone A, Le Large TY, Funel N, Kazemier G, Peters GJ, Vasile E and Giovannetti E: FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer. World J Gastroenterol. 22:6987–7005. 2016. View Article : Google Scholar : PubMed/NCBI
19	Goel G and Sun W: Novel approaches in the management of pancreatic ductal adenocarcinoma: Potential promises for the future. J Hematol Oncol. 8:442015. View Article : Google Scholar : PubMed/NCBI
20	Ghosn M, Ibrahim T, Assi T, El Rassy E, Kourie HR and Kattan J: Dilemma of first line regimens in metastatic pancreatic adenocarcinoma. World J Gastroenterol. 22:10124–10130. 2016. View Article : Google Scholar : PubMed/NCBI
21	Mu J, Liu T, Jiang L, Wu X, Cao Y, Li M, Dong Q, Liu Y and Xu H: The traditional Chinese medicine baicalein potently inhibits gastric cancer cells. J Cancer. 7:453–461. 2016. View Article : Google Scholar : PubMed/NCBI
22	Zheng YH, Yin LH, Grahn TH, Ye AF, Zhao YR and Zhang QY: Anticancer effects of baicalein on hepatocellular carcinoma cells. Phytother Res. 28:1342–1348. 2014. View Article : Google Scholar : PubMed/NCBI
23	Seo MJ, Choi HS, Jeon HJ, Woo MS and Lee BY: Baicalein inhibits lipid accumulation by regulating early adipogenesis and m-TOR signaling. Food Chem Toxicol. 67:57–64. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wang CZ, Calway TD, Wen XD, Smith J, Yu C, Wang Y, Mehendale SR and Yuan CS: Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway. Int J Oncol. 42:1018–1026. 2013. View Article : Google Scholar : PubMed/NCBI
25	Kosmidis C, Sapalidis K, Kotidis E, Mixalopoulos N, Zarogoulidis P, Tsavlis D, Baka S, Man YG and Kanellos J: Pancreatic cancer from bench to bedside: Molecular pathways and treatment options. Ann Transl Med. 4:1652016. View Article : Google Scholar : PubMed/NCBI
26	Lemstrova R, Melichar B and Mohelnikova-Duchonova B: Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer. Cancer Chemother Pharmacol. 78:1101–1111. 2016. View Article : Google Scholar : PubMed/NCBI
27	Gong WY, Zhao ZX, Liu BJ, Lu LW and Dong JC: Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors. Eur J Med Chem. 126:844–852. 2017. View Article : Google Scholar
28	Li J, Ma J, Wang KS, Mi C, Wang Z, Piao LX, Xu GH, Li X, Lee JJ and Jin X: Baicalein inhibits TNF-α-induced NF-κB activation and expression of NF-κB-regulated target gene products. Oncol Rep. 36:2771–2776. 2016. View Article : Google Scholar : PubMed/NCBI
29	Choi EO, Park C, Hwang HJ, Hong SH, Kim GY, Cho EJ, Kim WJ and Choi YH: Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells. Int J Oncol. 49:1009–1018. 2016. View Article : Google Scholar : PubMed/NCBI