Puerarin inhibits non-small cell lung cancer cell growth via the induction of apoptosis

Hu,Yefang; Li,Xi; Lin,Ling; Liang,Siting; Yan,Jian

doi:10.3892/or.2018.6234

Puerarin inhibits non-small cell lung cancer cell growth via the induction of apoptosis

Authors:
- Yefang Hu
- Xi Li
- Ling Lin
- Siting Liang
- Jian Yan
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Affiliations: Pharmacy Department, Guilin Traditional Chinese Medicine Hospital, Guilin, Guangxi 541002, P.R. China, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, Guangxi 541004, P.R. China
Published online on: January 26, 2018 https://doi.org/10.3892/or.2018.6234
Pages: 1731-1738

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Abstract

Puerarin, an isoflavone isolated from Kudzu roots, has been demonstrated to have beneficial effect on cardiovascular and cerebral vascular diseases. Recently research has revealed that puerarin exerts an anticancer role in many different types of cancer. The aim of the present study was to investigate the antitumor effects of puerarin on non-small cell lung cancer (NSCLC). Treatment of puerarin significantly inhibited the growth of NSCLC cell lines as determined by CCK-8 kit in vitro. Flow cytometry results indicated that puerarin treatments promoted NSCLC cell apoptosis. This result was further confirmed by western blot analysis of expression levels of proteins involved in the mitochondrial-mediated apoptosis pathway. Moreover, puerarin slightly induced cell autophagy through the PI3K/Akt and MAPK/Erk1/2 signaling pathways. In addition, a tumor xenograft model was established using nude mice, and the inhibitory effects on tumor growth by puerarin treatment were also detected. Taken together, these findings demonstrated that puerarin has anticancer activities and puerarin is a potential therapeutic agent for lung cancer.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Świątkowska B, Szubert Z, Sobala W and Szeszenia-Dąbrowska N: Predictors of lung cancer among former asbestos-exposed workers. Lung Cancer. 89:243–248. 2015. View Article : Google Scholar : PubMed/NCBI
3	Devesa SS, Bray F, Vizcaino AP and Parkin DM: International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 117:294–299. 2005. View Article : Google Scholar : PubMed/NCBI
4	Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ and Cronin KA: SEER Cancer Statistics Review, 1975–2012. National Cancer Institute; Bethesda, MD: http://seer.cancer.gov/csr/1975_2012/based on November 2014 SEER data submission, posted to the SEER web site. April. 2015
5	Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, et al CONCORD Working Group, : Global surveillance of cancer survival 1995–2009: Analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 385:977–1010. 2015. View Article : Google Scholar : PubMed/NCBI
6	Gupta SK: Role of Crizotinib in previously treated non-small-cell lung cancer. South Asian J Cancer. 3:138–140. 2014. View Article : Google Scholar : PubMed/NCBI
7	Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J and Johnson DH; Eastern Cooperative Oncology Group, : Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar : PubMed/NCBI
8	Angulo P, Kaushik G, Subramaniam D, Dandawate P, Neville K, Chastain K and Anant S: Natural compounds targeting major cell signaling pathways: A novel paradigm for osteosarcoma therapy. J Hematol Oncol. 10:102017. View Article : Google Scholar : PubMed/NCBI
9	Chanvorachote P, Chamni S, Ninsontia C and Phiboonchaiyanan PP: Potential anti-metastasis natural compounds for lung lancer. Anticancer Res. 36:5707–5717. 2016. View Article : Google Scholar : PubMed/NCBI
10	Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, Dharmarajan A, Kumar AP, Ramar PS, Looi CY, et al: Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin Cancer Biol 40–41. 1–47. 2016.
11	Pan MH, Lai CS, Wu JC and Ho CT: Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Mol Nutr Food Res. 55:32–45. 2011. View Article : Google Scholar : PubMed/NCBI
12	Guo XF, Yang ZR, Wang J, Lei XF, Lv XG and Dong WG: Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma. Mol Med Rep. 11:2562–2568. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zeng YP, Yang ZR, Guo XF, Jun W and Dong WG: Synergistic effect of puerarin and 5-fluorouracil on hepatocellular carcinoma. Oncol Lett. 8:2436–2442. 2014. View Article : Google Scholar : PubMed/NCBI
14	Zhang SF, Wang XL, Yang XQ and Chen N: Autophagy-associated targeting pathways of natural products during cancer treatment. Asian Pac J Cancer Prev. 15:10557–10563. 2014. View Article : Google Scholar : PubMed/NCBI
15	Yanagihara K, Ito A, Toge T and Numoto M: Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res. 53:5815–5821. 1993.PubMed/NCBI
16	Tian F, Xu LH, Zhao W, Tian LJ and Ji XL: The optimal therapeutic timing and mechanism of puerarin treatment of spinal cord ischemia-reperfusion injury in rats. J Ethnopharmacol. 134:892–896. 2011. View Article : Google Scholar : PubMed/NCBI
17	Wong KH, Li GQ, Li KM, Razmovski-Naumovski V and Chan K: Kudzu root: Traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases. J Ethnopharmacol. 134:584–607. 2011. View Article : Google Scholar : PubMed/NCBI
18	Yuan Y, Zong J, Zhou H, Bian ZY, Deng W, Dai J, Gan HW, Yang Z, Li H and Tang QZ: Puerarin attenuates pressure overload-induced cardiac hypertrophy. J Cardiol. 63:73–81. 2014. View Article : Google Scholar : PubMed/NCBI
19	Yeung DK, Leung SW, Xu YC, Vanhoutte PM and Man RY: Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery. Eur J Pharmacol. 552:105–111. 2006. View Article : Google Scholar : PubMed/NCBI
20	Yu Z and Li W: Induction of apoptosis by puerarin in colon cancer HT-29 cells. Cancer Lett. 238:53–60. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Ma Y, Zheng Y, Song J, Yang X, Bi C, Zhang D and Zhang Q: In vitro and in vivo anticancer activity of a novel puerarin nanosuspension against colon cancer, with high efficacy and low toxicity. Int J Pharm. 441:728–735. 2013. View Article : Google Scholar : PubMed/NCBI
22	Zhang WG, Liu XF, Meng KW and Hu SY: Puerarin inhibits growth and induces apoptosis in SMMC-7721 hepatocellular carcinoma cells. Mol Med Rep. 10:2752–2758. 2014. View Article : Google Scholar : PubMed/NCBI
23	Lin YJ, Hou YC, Lin CH, Hsu YA, Sheu JJ, Lai CH, Chen BH, Lee Chao PD, Wan L and Tsai FJ: Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Biochem Biophys Res Commun. 378:683–688. 2009. View Article : Google Scholar : PubMed/NCBI
24	National Research Council of the National Academies, . Guide for the Care and Use of Laboratory Animals: 2011. The National Academies Press; Washington, DC: 2011
25	Ma Y, Gai Y, Yan J, Li J and Zhang Y: Puerarin attenuates anoxia/reoxygenation injury through enhancing Bcl-2 associated athanogene 3 Expression, a modulator of apoptosis and autophagy. Med Sci Monit. 22:977–983. 2016. View Article : Google Scholar : PubMed/NCBI
26	Liu B, Wu Z, Li Y, Ou C, Huang Z, Zhang J, Liu P, Luo C and Chen M: Puerarin prevents cardiac hypertrophy induced by pressure overload through activation of autophagy. Biochem Biophys Res Commun. 464:908–915. 2015. View Article : Google Scholar : PubMed/NCBI
27	Wei SY, Chen Y and Xu XY: Progress on the pharmacological research of puerarin: A review. Chin J Nat Med. 12:407–414. 2014.PubMed/NCBI
28	Han J, Yu CQ and Shen W: Inhibitory effects of puerarin on invasion and metastasis of oophoroma cells HO-8910. Zhongguo Zhong Xi Yi Jie He Za Zhi. 29:632–635. 2009.(In Chinese). PubMed/NCBI
29	Zhu G, Wang X, Wu S and Li Q: Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP⁺-induced human neuroblastoma SH-SY5Y cell death. Neurochem Int. 60:400–408. 2012. View Article : Google Scholar : PubMed/NCBI
30	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
31	Oltvai ZN, Milliman CL and Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:609–619. 1993. View Article : Google Scholar : PubMed/NCBI
32	Choi YH, Kong KR, Kim YA, Jung KO, Kil JH, Rhee SH and Park KY: Induction of Bax and activation of caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells. Int J Oncol. 23:1657–1662. 2003.PubMed/NCBI
33	Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y and Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI
34	Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, et al: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12:1–222. 2016. View Article : Google Scholar : PubMed/NCBI