Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis

Guan,Tingting; Yang,Yanmin

doi:10.3892/mmr.2013.1800

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis

Authors:
- Tingting Guan
- Yanmin Yang
View Affiliations

Affiliations: Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: November 14, 2013 https://doi.org/10.3892/mmr.2013.1800
Pages: 144-148

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

Recently, traditional Chinese medicine has gained attention for its potential use as a chemotherapeutic agent. Pseudolaric acid B (PAB) is a diterpene acid isolated from Pseudolarix kaempferi and possesses antifungal, antimicrobial, antifertility and antiangiogenic properties. It was also reported that PAB may inhibit proliferation and induce apoptosis in various types of cancer. However, its effects on A549 lung cancer cells remain to be determined. The present study aimed to determine the potential roles of PAB in the proliferation and apoptosis of A549 cells. The results showed that PAB inhibited A549 cell proliferation in a time‑ and dose‑dependent manner. Fluorescence microscopy results showed that cells treated with 20 µmol/l PAB for 24 h exhibited karyorrhexis and apoptotic body formation. In addition, A549 cells were treated with 5, 10, 20, 40 or 80 µmol/l PAB for 24 h and apoptosis was analyzed using Annexin‑V/propidium iodide kit. The apoptosis rates were 8.95, 18.71, 24.66, 35.02 and 43.64%, respectively, in PAB‑treated cells and 0.80% in the control group. Furthermore, western blot analysis showed that PAB treatment upregulated the protein levels of Bax, Bad and downregulated Bcl‑2 and Bcl‑xl expression. In conclusion, PAB may serve as a potent chemotherapeutic agent against human lung cancer.

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	Erridge SC, Møller H, Price A and Brewster D: International comparisons of survival from lung cancer: pitfalls and warnings. Nat Clin Pract Oncol. 4:570–577. 2007. View Article : Google Scholar : PubMed/NCBI
3	Efferth T, Li PC, Konkimalla VS and Kaina B: From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 13:353–361. 2007. View Article : Google Scholar : PubMed/NCBI
4	Harvey AL: Natural products in drug discovery. Drug Discov Today. 13:894–901. 2008. View Article : Google Scholar : PubMed/NCBI
5	Hanson JR: Diterpenoids. Nat Product Rep. 26:1156–1171. 2009. View Article : Google Scholar : PubMed/NCBI
6	Cheng SY, Chuang CT, Wang SK, et al: Antiviral and anti-inflammatory diterpenoids from the soft coral Sinularia gyrosa. J Nat Prod. 73:1184–1187. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hsieh TC, Wijeratne EK, Liang JY, et al: Differential control of growth, cell cycle progression, and expression of NF-kappa B in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb Rabdosia rubescens. Biochem Biophys Res Commun. 337:224–231. 2005. View Article : Google Scholar : PubMed/NCBI
8	Yang SP, Dong L, Wang Y, et al: Antifungal diterpenoids of Pseudolarix kaempferi, and their structure-activity relationship study. Bioorg Med Chem. 11:4577–4584. 2003.PubMed/NCBI
9	Duan HQ, Takaishi Y, Momota H, et al: Immunosuppressive diterpenoids from Tripterygium wilfordii. J Nat Prod. 62:1522–1525. 1999. View Article : Google Scholar
10	Trost BM, Waser J and Meyer A: Total synthesis of (−)-pseudolaric acid B. J Am Chem Soc. 130:16424–16434. 2008.
11	Li E, Clark AM and Hufford CD: Antifungal evaluation of pseudolaric acid B, a major constituent of Pseudolarix kaempferi. J Nat Prod. 58:57–67. 1995. View Article : Google Scholar : PubMed/NCBI
12	Liu B, Chen H, Lei ZY, Yu PF and Xiong B: Studies on anti-tumour activities of pseudolaric acid-B (PLAB) and its mechanism of action. J Asian Nat Prod Res. 8:241–252. 2006. View Article : Google Scholar : PubMed/NCBI
13	Li T, Wong VK, Yi XQ, et al: Pseudolaric acid B suppresses T lymphocyte activation through inhibition of NF-kappa B signaling pathway and p38 phosphorylation. J Cell Biochem. 108:87–95. 2009. View Article : Google Scholar : PubMed/NCBI
14	Meng AG and Jiang LL: Pseudolaric acid B-induced apoptosis through p53-dependent pathway in human gastric carcinoma cells. J Asian Nat Prod Res. 11:142–152. 2009. View Article : Google Scholar : PubMed/NCBI
15	Li MH, Miao ZH, Tan WF, et al: Pseudolaric acid B inhibits angiogenesis and reduces hypoxia-inducible factor 1alpha by promoting proteasome-mediated degradation. Clin Cancer Res. 10:8266–8274. 2004. View Article : Google Scholar : PubMed/NCBI
16	Gong XF, Wang MW, Wu Z, et al: Pseudolaric acid B induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells. Exp Mol Med. 36:551–556. 2004. View Article : Google Scholar : PubMed/NCBI
17	Gong XF, Wang MW, Tashiro S, et al: Involvement of JNK-initiated p53 accumulation and phosphorylation of p53 in pseudolaric acid B induced cell death. Exp Mol Med. 38:428–434. 2006. View Article : Google Scholar : PubMed/NCBI
18	Gong XF, Wang MW, Tashiro S, et al: Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human melanoma A375-S2 cells. Arch Pharm Res. 28:68–72. 2005. View Article : Google Scholar : PubMed/NCBI
19	Li KS, Gu XF, Li P, et al: Effect of pseudolaric acid B on gastric cancer cells: inhibition of proliferation and induction of apoptosis. World J Gastroenterol. 11:7555–7559. 2005.PubMed/NCBI
20	Wu WY, Guo HZ, Qu GQ, et al: Mechanisms of pseudolaric acid B-induced apoptosis in Bel-7402 cell lines. Am J Chin Med. 34:887–899. 2006. View Article : Google Scholar : PubMed/NCBI
21	Yu JH, Cui Q, Jiang YY, et al: Pseudolaric acid B induces apoptosis, senescence, and mitotic arrest in human breast cancer MCF-7. Acta Pharmacol Sin. 28:1975–1983. 2007. View Article : Google Scholar : PubMed/NCBI
22	Yu JH, Wang HJ, Li XR, et al: Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells. Acta Pharmacol Sin. 29:1069–1076. 2008. View Article : Google Scholar : PubMed/NCBI
23	Yu J, Li X, Tashiro S, et al: Bcl-2 family proteins were involved in pseudolaric acid B-induced autophagy in murine fibrosarcoma L929 cells. J Pharmacol Sci. 107:295–302. 2008. View Article : Google Scholar : PubMed/NCBI
24	Qi M, Yao G, Fan S, et al: Pseudolaric acid B induces mitotic catastrophe followed by apoptotic cell death in murine fibrosarcoma L929 cells. Eur J Pharmacol. 683:16–26. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ma G, Chong L, Li XC, et al: Selective inhibition of human leukemia cell growth and induction of cell cycle arrest and apoptosis by pseudolaric acid B. J Cancer Res Clin Oncol. 136:1333–1340. 2010. View Article : Google Scholar : PubMed/NCBI
26	Zhao D, Lin F, Wu X, et al: Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells. Toxicol In Vitro. 26:595–602. 2012. View Article : Google Scholar : PubMed/NCBI
27	Khan M, Zheng B, Yi F, et al: Pseudolaric acid B induces caspase-dependent and caspase-independent apoptosis in U87 glioblastoma cells. Evid Based Complement Alternat Med. 2012:9575682012.PubMed/NCBI
28	Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 267:1456–1462. 1995. View Article : Google Scholar : PubMed/NCBI
29	Lowe SW and Lin AW: Apoptosis in cancer. Carcinogenesis. 21:485–495. 2000. View Article : Google Scholar
30	Huang DM, Shen YC, Wu C, et al: Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane diterpenoids in human prostate cancer PC-3 cells. Eur J Pharmacol. 503:17–24. 2004. View Article : Google Scholar : PubMed/NCBI
31	Cheung HY, Cheung SH, Li JL, et al: Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells. Planta Med. 71:1106–1111. 2005.PubMed/NCBI
32	Korsmeyer SJ: BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 59(Suppl 7): 1693s–1700s. 1999.PubMed/NCBI
33	Jiao Y, Ge CM, Meng QH, et al: Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin. 28:1045–1056. 2007. View Article : Google Scholar : PubMed/NCBI
34	Wang JB, Qi LL, Zheng SD and Wu TX: Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells. J Zhejiang Univ Sci B. 10:93–102. 2009. View Article : Google Scholar
35	Wu SJ, Ng LT, Lin DL, et al: Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway. Cancer Lett. 215:199–208. 2004. View Article : Google Scholar