Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (5): 533-538.doi: 10.3736/jcim20110511

• Original Experimental Research • Previous Articles     Next Articles

Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Zhao-hui Chu1,2, Xiao-hua Liang1,2(), Xin-li Zhou1,2, Ruo-fan Huang1,2, Qiong Zhan1,2, Jing-wei Jiang1,2   

  1. 1. Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, China
    2. School of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Received:2010-12-18 Accepted:2010-12-27 Online:2011-05-20 Published:2011-05-15
  • Contact: Liang Xiao-hua

Objective: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
Methods: After treatment with 0, 1, 5, 10, 15 and 20 μmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 μmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis.
Results: Deguelin at doses of 5, 10, 15 and 20 μmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P<0.01). The inhibitory effect was more marked with increasing concentration and duration of treatment. There were statistical differences (P<0.05) among 5, 10, 15 and 20 μmol/L groups. However, 1 μmol/L of deguelin had no obvious effects on the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours, showing no significant difference compared with control group (P>0.05). Deguelin at doses of 5, 10, 15 and 20 μmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 μmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 μmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3β (GSK-3β) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 μmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins.
Conclusion: Deguelin can inhibit the phosphorylation of GSK-3β (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.

Key words: deguelin, 1-phosphatidylinositol 3-kinase, Akt, cell proliferation, apoptosis, MCF-7 cell line, in vitro



Figure 1

A poptotic morphology of MCF-7 cells after culturing with deguelin for 6 h (Transmission electron microscopy, ×10 000)"

Figure 2

Expressions of PI3K/Akt signaling pathway proteins in MCF-7 cells after culturing with deguelin for 6 h GAPDH: glyceraldehyde-3-phosphate dehydrogenase; p-PTEN: phosphorylated phosphatase and tensin homologue deleted on chromosome 10; p-PDK1: phosphorylated 3-phosphoinositide-dependent protein kinase 1; p-GSK-3β: phosphorylated glycogen synthase kinase-3β."

[1] Chun KH, Kosmeder JW 2nd, Sun S, Pezzuto JM, Lotan R, Hong WK, Lee HY .Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells[J]. J Natl Cancer Inst, 2003,95(4):291-302
doi: 10.1093/jnci/95.4.291
[2] Nair AS, Shishodia S, Ahn KS, Kunnumakkara AB, Sethi G, Aggarwal BB . Deguelin, an Akt inhibitor, suppresses IkappaBalpha kinase activation leading to suppression of NF-kappaB-regulated gene expression, potentiation of apoptosis, and inhibition of cellular invasion[J]. J Immunol, 2006,177(8):5612-5622
doi: 10.4049/jimmunol.177.8.5612
[3] Bortul R, Tazzari PL, Billi AM, Tabellini G, Mantovani I, Cappellini A, Grafone T, Martinelli G, Conte R, Martelli AM . Deguelin, A PI3K/AKT inhibitor, enhances chemosensitivity of leukaemia cells with an active PI3K/AKT pathway[J]. Br J Haematol, 2005,129(5):677-686
doi: 10.1111/bjh.2005.129.issue-5
[4] Geeraerts B, Vanhoecke B, Vanden Berghe W, Philippé J, Offner F, Deforce D . Deguelin inhibits expression of IkappaBalpha protein and induces apoptosis of B-CLL cells in vitro[J]. Leukemia, 2007,21(8):1610-1618
doi: 10.1038/sj.leu.2404788
[5] Yi T, Li H, Wang X, Wu Z . Enhancement radiosensitization of breast cancer cells by deguelin[J]. Cancer Biother Radiopharm, 2008,23(3):355-362
doi: 10.1089/cbr.2007.0452 pmid: 18593368
[6] Jin Q, Feng L, Behrens C, Bekele BN, Wistuba II, Hong WK, Lee HY . Implication of AMP-activated protein kinase and Akt-regulated survivin in lung cancer chemopreventive activities of deguelin[J]. Cancer Res, 2007,67(24):11630-11639
doi: 10.1158/0008-5472.CAN-07-2401
[7] Tuoknaga E, Kimura Y, Mashino K, Oki E, Kataoka A, Ohno S, Morita M, Kakeji Y, Baba H, Maehara Y . Activation of PI3K/Akt signaling and hormone resistance in breast cancer[J]. Breast Cancer, 2006,13(2):137-144
doi: 10.2325/jbcs.13.137 pmid: 16755107
[8] Li X, Lu Y, Liang K, Liu B, Fan Z . Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells[J]. Breast Cancer Res, 2005,7(5):R589-R597
doi: 10.1186/bcr1259
[9] Soderlund K, Pérez-Tenorio G, Stal O . Activation of the phosphatidylinositol 3-kinase/Akt pathway prevents radiation-induced apoptosis in breast cancer cells[J]. Int J Oncol, 2005,26(1):25-32
[10] Casamayor A, Morrice NA, Alessi DR . Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo[J]. Biochem J, 1999,342(Pt 2):287-292
doi: 10.1042/bj3420287
[11] Das S, Dixon JE, Cho W . Membrane-binding and activation mechanism of PTEN[J]. Proc Natl Acad Sci U S A, 2003,100(13):7491-7496
doi: 10.1073/pnas.0932835100 pmid: 12808147
[12] Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA . Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B[J]. Nature, 1995,378(6559):785-789
doi: 10.1038/378785a0 pmid: 8524413
[13] Diehl JA, Cheng M, Roussel MF, Sherr CJ . Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization[J]. Genes Dev, 1998,12(22):3499-3511
doi: 10.1101/gad.12.22.3499
[1] Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai. Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro. Journal of Integrative Medicine, 2022, 20(4): 365-375.
[2] Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine, 2022, 20(2): 163-172.
[3] Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim. Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
. Journal of Integrative Medicine, 2022, 20(1): 65-72.
[4] Hyongjun Jeon, Hee-Young Kim, Chang-Hwan Bae, Yukyung Lee, Sungtae Koo, Seungtae Kim. Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells. Journal of Integrative Medicine, 2021, 19(6): 537-544.
[5] Tong Zhao, Bing-jie Guo, Chu-lan Xiao, Jiao-jiao Chen, Can Lü, Fan-fu Fang, Bai Li. Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway. Journal of Integrative Medicine, 2021, 19(5): 418-427.
[6] Qing-lan Wang, Yan-yan Tao, Hong-dong Xie, Cheng-hai Liu, Ping Liu. Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis. Journal of Integrative Medicine, 2020, 18(6): 505-513.
[7] Porwornwisit Tritripmongkol, Tullayakorn Plengsuriyakarn, Mayuri Tarasuk, Kesara Na-Bangchang. In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. Journal of Integrative Medicine, 2020, 18(4): 326-333.
[8] Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera. Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells. Journal of Integrative Medicine, 2020, 18(3): 242-252.
[9] Maged Mohamed Maher Abou-Hashem, Dina Mohamed Abo-elmatty, Noha Mostafa Mesbah, Ahmed Mohamed Abd EL-Mawgoud. Induction of sub-G0 arrest and apoptosis by seed extract of Moringa peregrina (Forssk.) Fiori in cervical and prostate cancer cell lines. Journal of Integrative Medicine, 2019, 17(6): 410-422.
[10] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Apirada Sucontphunt, Mattaka Khongkow, Thongchai Koobkokkruad, Nontima Vardhanabhuti. Flavonoids kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells. Journal of Integrative Medicine, 2019, 17(4): 288-295.
[11] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[12] Carlos R. Oliveira, Daniel G. Spindola, Daniel M. Garcia, Adolfo Erustes, Alexandre Bechara, Caroline Palmeira-dos-Santos, Soraya S. Smaili, Gustavo J.S. Pereira, André Hinsberger, Ezequiel P. Viriato, Maria Cristina Marcucci, Alexandra C.H.F. Sawaya, Samantha L. Tomaz, Elaine G. Rodrigues, Claudia Bincoletto. Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development. Journal of Integrative Medicine, 2019, 17(2): 132-140.
[13] Syed Nasir Abbas Bukhari, Fahad Hussain, Hnin Ei Thu, Zahid Hussain. Synergistic effects of combined therapy of curcumin and Fructus Ligustri Lucidi for treatment of osteoporosis: cellular and molecular evidence of enhanced bone formation. Journal of Integrative Medicine, 2019, 17(1): 38-45.
[14] Bruno José Martins Da Silva, Sandro Wilson Gomes Pereira, Ana Paula Drummond Rodrigues, José Luiz Martins Do Nascimento, Edilene Oliveira Silva. In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum. Journal of Integrative Medicine, 2018, 16(6): 404-410.
[15] Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan . Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 2018, 16(3): 147-152.
Full text



[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239