Apoptotic effect of gambogic acid in esophageal squamous cell carcinoma cells via suppression of the NF-κB pathway

Liu,Wen‑Yue; Wu,Xu; Liao,Cheng‑Quan; Shen,Jie; Li,Jun

doi:10.3892/ol.2016.4437

Apoptotic effect of gambogic acid in esophageal squamous cell carcinoma cells via suppression of the NF-κB pathway

Authors:
- Wen‑Yue Liu
- Xu Wu
- Cheng‑Quan Liao
- Jie Shen
- Jun Li
View Affiliations

Affiliations: Department of Thoracic and Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Cardiovascular Surgery, Yuebei People's Hospital, Shaoguan, Guangdong 512026, P.R. China, Department of Medical Records, Yuebei People's Hospital, Shaoguan, Guangdong 512026, P.R. China, Department of Thoracic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China
Published online on: April 14, 2016 https://doi.org/10.3892/ol.2016.4437
Pages: 3681-3685
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Despite extensive investigations of therapeutic improvements for surgical techniques, chemotherapy and chemoradiotherapy, esophageal squamous cell carcinoma (ESCC) remains one of the most aggressive forms of cancer, and the prognosis for patients with advanced ESCC remains poor. Therefore, effective therapies are urgently required in order to improve the prognosis of patients with ESCC. TE‑1 cells were treated with gambogic acid (GA), and then subjected to western blot analysis, TUNEL assay and caspase activity analysis. GA significantly induced apoptosis in ESCC TE‑1 cells. In addition, the antitumor activity of GA was accompanied by the decreased expression of phosphorylated‑protein kinase B (p‑AKT) and nuclear factor of κ light polypeptide gene enhancer in B‑cells 1 (NF‑κB). The inhibition of protein kinase B (AKT) and NF‑κB activation by chemical inhibitors augmented the apoptotic effect responses to GA in the TE‑1 cells. The pan‑caspase inhibitor z‑VAD‑fmk (zVAD) decreased GA‑induced apoptosis. Furthermore, zVAD attenuated GA‑induced growth inhibition in TE‑1 cells. GA induced apoptosis in ESCC TE‑1 via suppression of NF‑κB pathway. The findings of the present study may provide a novel insight into ESCC treatment.

View Figures

View References

1	Dawsey SP, Tonui S, Parker RK, Fitzwater JW, Dawsey SM, White RE and Abnet CC: Esophageal cancer in young people: A case series of 109 cases and review of the literature. PLoS One. 5:e140802010. View Article : Google Scholar : PubMed/NCBI
2	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
3	Ando N, Ozawa S, Kitagawa Y, Shinozawa Y and Kitajima M: Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 232:225–232. 2000. View Article : Google Scholar : PubMed/NCBI
4	Strong VE, D'Amico TA, Kleinberg L and Ajani J: Impact of the 7th Edition AJCC staging classification on the NCCN clinical practice guidelines in oncology for gastric and esophageal cancers. J Natl Compr Canc Netw. 11:60–66. 2013.PubMed/NCBI
5	Iwase H, Shimada M, Tsuzuki T, Hirashima N, Okeya M, Hibino Y, Ryuge N, Yokoi M, Kida Y, Kuno T, et al: Concurrent chemoradiotherapy with a novel fluoropyrimidine, S-1 and cisplatin for locally advanced esophageal cancer: Long-term results of a phase II trial. Oncology. 84:342–349. 2013. View Article : Google Scholar : PubMed/NCBI
6	Zhao L, Guo QL, You QD, Wu ZQ and Gu HY: Gambogic acid induces apoptosis and regulates expressions of Bax and Bcl-2 protein in human gastric carcinoma MGC-803 cells. Biol Pharm Bull. 27:998–1003. 2004. View Article : Google Scholar : PubMed/NCBI
7	Gu H, Rao S, Zhao J, Wang J, Mu R, Rong J, Tao L, Qi Q, You Q and Guo Q: Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells. J Cancer Res Clin Oncol. 135:1777–1782. 2009. View Article : Google Scholar : PubMed/NCBI
8	Xie H, Qin YX, Zhou YL, Tong LJ, Lin LP, Geng MY, Duan WH and Ding J: GA3, a new gambogic acid derivative, exhibits potent antitumor activities in vitro via apoptosis-involved mechanisms. Acta Pharmacol Sin. 30:346–354. 2009. View Article : Google Scholar : PubMed/NCBI
9	Guo QL, You QD, Wu ZQ, Yuan ST and Zhao L: General gambogic acids inhibited growth of human hepatoma SMMC-7721 cells in vitro and in nude mice. Acta Pharmacol Sin. 25:769–774. 2004.PubMed/NCBI
10	Colo GP, Rubio MF, Nojek IM, Werbajh SE, Echeverría PC, Alvarado CV, Nahmod VE, Galigniana MD and Costas MA: The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action. Oncogene. 27:2430–2444. 2008. View Article : Google Scholar : PubMed/NCBI
11	Nicholson DW and Thornberry NA: Caspases: Killer proteases. Trends Biochem Sci. 22:299–306. 1997. View Article : Google Scholar : PubMed/NCBI
12	Savill J and Fadok VA: Corpse clearance defines the meaning of cell death. Nature. 407:784–788. 2000. View Article : Google Scholar : PubMed/NCBI
13	Danial NN and Korsmeyer SJ: Cell death: Critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI
14	Gu HY, Guo QL, You QD, Liu W, Qi Q, Li Z, Yuan ST and Zhang K: Gambogic acid inducing apoptosis in human hepatoma SMMC-7721 cells with p53 and Bax up-regulated. Chin J Nat Med. 3:169–171. 2005.
15	Xu J, Zhou M, Ouyang J, Wang J, Zhang Q, Xu Y, Xu Y, Zhang Q, Xu X and Zeng H: Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cells. Zhongguo Aizheng Yanjiu (Yingwenban). 25:183–191. 2013.
16	Luo GX, Cai J, Lin JZ, Luo WS, Luo HS, Jiang YY and Zhang Y: Autophagy inhibition promotes gambogic acid-induced suppression of growth and apoptosis in glioblastoma cells. Asian Pac J Cancer Prev. 13:6211–6216. 2012. View Article : Google Scholar : PubMed/NCBI
17	Shi SQ and Cao HM: Shikonin promotes autophagy in BXPC-3 human pancreatic cancer cells through the PI3K/Akt signaling pathway. Oncol Lett. 8:1087–1089. 2014.PubMed/NCBI
18	Zhang BC: Treatment of symptoms and root causes of disease-management of the top ten symptoms in cancer patients. Fang Ai Tian Di. 20:17–18. 2007.
19	Smith ME and Bauer-Wu S: Traditional Chinese Medicine for cancer-related symptoms. Semin Oncol Nurs. 28:64–97. 2012. View Article : Google Scholar : PubMed/NCBI
20	Wang S, Wu X, Tan M, Gong J, Tan W, Bian B, Chen M and Wang Y: Fighting fire with fire: Poisonous Chinese herbal medicine for cancer therapy. J Ethnopharmacol. 140:33–45. 2012. View Article : Google Scholar : PubMed/NCBI