Similar articles

Abstract: soybean isoflavones have been one of the potential preventive candidates for antitumor research in recent years. In this paper, we first studied the transformation of soybean isoflavones with the homogenized slurry of Ganoderma lucidum. The resultant transformed products (TSI) contained (703.21±4.35) mg/g of genistein, with transformed rates of 96.63% and 87.82% of daidzein and genistein, respectively, and TSI also could enrich the bioactive metabolites of G. lucidum. The antitumor effects of TSI on human colorectal cancer cell line HTL-9, human breast cancer cell line MCF-7, and human immortalized gastric epithelial cell line GES-1 were also studied. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay showed that TSI could dramatically reduce the viability rates of HTL-9 cells and MCF-7 cells without detectable cytotoxicity on GES-1 normal cells when the TSI concentration was lower than 100 μg/ml. With 100 μg/ml of TSI, HTL-9 cells were arrested in the G1 phase, and late-apoptosis was primarily induced, accompanied with partial early-apoptosis. TSI could induce primarily early-apoptosis by arresting cells in the G1 phase of MCF-7 cells. For HTL-9 cells, Western-blot and reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that TSI (100 μg/ml) can up-regulate the expression of Bax, Caspase-3, Caspase-8, and cytochrome c (Cyto-c), indicating that TSI could induce cell apoptosis mainly through the mitochondrial pathway. In addition, the expression of p53 was up-regulated, while the expression of Survivin and nuclear factor κB (NF-κB) was down-regulated. All these results showed that TSI could induce apoptosis of HTL-9 cells by the regulation of multiple apoptosis-related genes.

灵芝菌生物转化大豆异黄酮及其产物对结直肠癌细胞HTL-9的体外凋亡诱导研究

[1]Al-Fatlawi, A.A., Abbas, A., Zafaryab, M., et al., 2014. Rhein induced cell death and apoptosis through caspase dependent and associated with modulation of p53, Bcl-2/Bax ratio in human cell lines. Int. J. Pharm. Pharmaceut. Sci., 6(2):515-519.

[2]Andlauer, W., Kolb, J., Stehle, P., et al., 2000. Absorption and metabolism of genistein in isolated rat small intestine. J. Nutr., 130(4):843-846.

[3]Baglia, M.L., Gu, K., Zhang, X., et al., 2015. Soy isoflavone intake and bone mineral density in breast cancer survivors. Cancer Causes Control, 26(4):571-580.

[4]Banerjee, S., Ali, S., Azmi, A., et al., 2012. Abstract 2698: improved therapeutic activity of isoflavone-G2535 and docetaxel combination in hormone refractory prostate cancer. Cancer Res., 72(8 Suppl.):2698.

[5]Budhathoki, S., Joshi, A.M., Ohnaka, K., et al., 2011. Soy food and isoflavone intake and colorectal cancer risk: the fukuoka colorectal cancer study. Scand. J. Gastroenterol., 46(2):165-172.

[6]Chen, J., Hou, R., Zhang, X., et al., 2014. Calycosin suppresses breast cancer cell growth via ERβ-dependent regulation of IGF-1R, p38 MAPK and PI3K/Akt pathways. PLoS ONE, 9(3):e91245.

[7]Choi, E.J., Kim, G.H., 2013. Antiproliferative activity of daidzein and genistein may be related to ERα/c-erbB-2 expression in human breast cancer cells. Mol. Med. Rep., 7(3):781-784.

[8]Cotrim, C.Z., Fabris, V., Doria, M.L., et al., 2013. Estrogen receptor β growth-inhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells. Oncogene, 32(19):2390-2402.

[9]Cui, M.L., Yang, H.Y., He, G.Q., 2015. Submerged fermentation production and characterization of intracellular triterpenoids from Ganoderma lucidum using HPLC-ESI-MS. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 16(12):998-1010.

[10]Ewe, J.A., Wan-Abdullah, W.N., Alias, A.K., et al., 2012. Enhanced growth of lactobacilli and bioconversion of isoflavones in biotin-supplemented soymilk by electroporation. Int. J. Food Sci. Nutr., 63(5):580-596.

[11]Ferlay, J., Soerjomataram, I., Dikshit, R., et al., 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 136(5):E359-E386.

[12]Gong, Y., Li, Y., Lu, Y., et al., 2011. Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice. Int. J. Cancer, 129(5):1042-1052.

[13]Guo, X.Y., Liu, D., Ye, M., et al., 2013. Structural characterization of minor metabolites and pharmacokinetics of ganoderic acid C2 in rat plasma by HPLC coupled with electrospray ionization tandem mass spectrometry. J. Pharm. Biomed. Anal., 75:64-73.

[14]Handa, C.L., Couto, U.R., Vicensoti, A.H., et al., 2014. Optimisation of soy flour fermentation parameters to produce beta-glucosidase for bioconversion into aglycones. Food Chem., 152:56-65.

[15]Hati, S., Vij, S., Singh, B.P., et al., 2015. β-Glucosidase activity and bioconversion of isoflavones during fermentation of soymilk. J. Sci. Food Agric., 95(1):216-220.

[16]Hsin, I.L., Ou, C.C., Wu, M.F., et al., 2015. GMI, an immunomodulatory protein from Ganoderma microsporum, potentiates cisplatin-induced apoptosis via autophagy in lung cancer cells. Mol. Pharm., 12(5):1534-1543.

[17]Indran, I.R., Tufo, G., Pervaiz, S., et al., 2011. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. BBA-Bioenergetics, 1807(6):735-745.

[18]Kang, D., Mutakin, M., Levita, J., 2015. Computational study of triterpenoids of Ganoderma lucidum with aspartic protease enzymes for discovering HIV-1 and plasmepsin inhibitors. Int. J. Chem., 7(1):62-68.

[19]Keypour, S., Rafati, H., Riahi, H., et al., 2010. Qualitative analysis of ganoderic acids in Ganoderma lucidum from Iran and China by RP-HPLC and electrospray ionisation-mass spectrometry (ESI-MS). Food Chem., 119(4):1704-1708.

[20]Kim, H.M., Paik, S.Y., Ra, K.S., et al., 2006. Enhanced production of exopolysaccharides by fed-batch culture of Ganoderma resinaceum DG-6556. J. Microbiol., 44(2):233-242.

[21]Kurahashi, N., Iwasaki, M., Sasazuki, S., et al., 2007. Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol. Biomarkers Prev., 16(3):538-545.

[22]Lee, S.Y., Rhee, H.M., 1990. Cardiovascular effects of mycelium extract of Ganoderma lucidum: inhibition of sympathetic outflow as a mechanism of its hypotensive action. Chem. Pharm. Bull., 38(5):1359-1364.

[23]Li, Y., Kong, D., Ahmad, A., et al., 2012a. Epigenetic deregulation of miR-29a and miR-1256 by isoflavone contributes to the inhibition of prostate cancer cell growth and invasion. Epigenetics, 7(8):940-949.

[24]Li, Y., Kong, D., Ahmad, A., et al., 2012b. Targeting bone remodeling by isoflavone and 3,3’-diindolylmethane in the context of prostate cancer bone metastasis. PLoS ONE, 7(3):e33011.

[25]Lim, J.C.W., Chan, T.K., Ng, D.S., et al., 2012. Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clin. Exp. Pharmacol. Physiol., 39(3):300-310.

[26]Liu, F., Bardhan, K., Yang, D., et al., 2012. NF-κB directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. J. Biol. Chem., 287(30):25530-25540.

[27]Liu, J., Zhang, C., Hu, W., et al., 2015. Tumor suppressor p53 and its mutants in cancer metabolism. Cancer Lett., 356(2):197-203.

[28]Loganathan, J., Jiang, J., Smith, A., et al., 2014. The mushroom Ganoderma lucidum suppresses breast-to-lung cancer metastasis through the inhibition of pro-invasive genes. Int. J. Oncol., 44(6):2009-2015.

[29]Maitan-Alfenas, G.P., Lorena, G.A., de Almeida, M.N., et al., 2014. Hydrolysis of soybean isoflavones by Debaryomyces hansenii UFV-1 immobilised cells and free β-glucosidase. Food Chem., 146:429-436.

[30]Mayola, E., Gallerne, C., Esposti, D.D., et al., 2011. Withaferin a induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2. Apoptosis, 16(10):1014-1027.

[31]Mense, S.M., Hei, T.K., Ganju, R.K., et al., 2008. Phytoestrogens and breast cancer prevention: possible mechanisms of action. Environ. Health Perspect., 116(4):426-433.

[32]Miranda, C.F., Morales-Cruz, M., Suarez, B., et al., 2014. Effect of cytochrome c modification with co-polymer on its apoptotic activity for cancer treatment (LB248). FASEB J., 28(1 Suppl.):248.

[33]Munck, L., Jorgensen, K.G., Ruud-Hansen, J., et al., 1989. The EBC methods for determination of high molecular weight β-glucan in barley, malt, wort and beer. J. Inst. Brewing, 95(2):79-82.

[34]Ollberding, N.J., Lim, U., Wilkens, L.R., et al., 2012. Legume, soy, tofu, and isoflavone intake and endometrial cancer risk in postmenopausal women in the multiethnic cohort study. J. Natl. Cancer Inst., 104(1):67-76.

[35]Prietsch, R.F., Monte, L.G., da Silva, F.A., et al., 2014. Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes. Mol. Cell Biochem., 390(1-2):235-242.

[36]Priyadarsini, R.V., Murugan, R.S., Maitreyi, S., et al., 2010. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol., 649(1-3):84-91.

[37]Selent, J., Kaczor, A.A., Guixa-Gonzalez, R., et al., 2013. Rational design of the survivin/CDK4 complex by combining protein-protein docking and molecular dynamics simulations. J. Mol. Model., 19(4):1507-1514.

[38]Srivastava, K., Singh, A.K., Khan, K., et al., 2014. Assessment of enhancement of peak bone gain by isoflavone enriched standardized soy extract in female rats. J. Funct. Foods, 7:314-321.

[39]Suarez-Jimenez, G.M., Burgos-Hernandez, A., Ezquerra-Brauer, J.M., 2012. Bioactive peptides and depsipeptides with anticancer potential: sources from marine animals. Marine Drugs, 10(12):963-986.

[40]Szliszka, E., Czuba, Z.P., Sędek, L., et al., 2011. Enhanced TRAIL-mediated apoptosis in prostate cancer cells by the bioactive compounds neobavaisoflavone and psoralidin isolated from Psoralea corylifolia. Pharm. Rep., 63(1):139-148.

[41]Tang, W., Liu, J.W., Zhao, W.M., et al., 2006. Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci., 80(3):205-211.

[42]Thomas, S., Quinn, B.A., Das, S.K., et al., 2013. Targeting the Bcl-2 family for cancer therapy. Exp. Opin. Therapeut. Tar., 17(1):61-75.

[43]Titiek, F., Umar, S., Cahyanto, M., et al., 2013. Effect of indigenous lactic acid bacteria fermentation on enrichment of isoflavone and antioxidant properties of kerandang (Canavalia virosa) extract. Int. Food Res. J., 20(5):2945-2950.

[44]Tse, G., Eslick, G.D., 2016. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. Eur. J. Nutr., 55(1):63-73.

[45]Tsuboy, M.S., Marcarini, J.C., de Souza, A.O., et al., 2014. Genistein at maximal physiologic serum levels induces G0/G1 arrest in MCF-7 and HB4a cells, but not apoptosis. J. Med. Food, 17(2):218-225.

[46]van Meerloo, J., Kaspers, G.J., Cloos, J., 2011. Cell sensitivity assays: the MTT assay. In: Cree, I. (Ed.), Cancer Cell Culture. Methods in Molecular Biology (Methods and Protocols), Vol. 731. Humana Press, p.237-245.

[47]Varfolomeev, E., Goncharov, T., Vucic, D., 2015. Roles of c-IAP proteins in TNF receptor family activation of NF-κB signaling. In: May, M. (Ed.), NF-κ B. Methods in Molecular Biology, Vol. 1280. Humana Press, New York, p.269-282.

[48]Wei, J., Bhatt, S., Chang, L.M., et al., 2012. Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function. PLoS ONE, 7(10):e47979.

[49]Xu, C.F., Wu, A.R., Zhu, H., et al., 2013. Melatonin is involved in the apoptosis and necrosis of pancreatic cancer cell line SW-1990 via modulating of Bcl-2/Bax balance. Biomed. Pharmacother., 67(2):133-139.

[50]Yan, L., Spitznagel, E.L., Bosland, M.C., 2010. Soy consumption and colorectal cancer risk in humans: a meta-analysis. Cancer Epidem. Biomar. Prev., 19(1):148-158.

[51]Yeo, S.K., Liong, M.T., 2010. Angiotensin I-converting enzyme inhibitory activity and bioconversion of isoflavones by probiotics in soymilk supplemented with prebiotics. Int. J. Food Sci. Nutr., 61(2):161-181.

[52]Yeom, S.J., Kim, B.N., Kim, Y.S., et al., 2012. Hydrolysis of isoflavone glycosides by a thermostable beta-glucosidase from Pyrococcus furiosus. J. Agric. Food Chem., 260(6):1535-1541.

[53]Yin, L.J., Tai, H.M., Lee, H.H., et al., 2014. Proteolysis and lactobacillus fermentation effects on the isoflavones transformation and removal of anti-nutritional factors of soy bean. J. Mar. Sci. Technol., 22(4):525-530.

[54]Zhao, W., Xu, J.W., Zhong, J.J., 2011. Enhanced production of ganoderic acids in static liquid culture of Ganoderma lucidum under nitrogen-limiting conditions. Bioresour. Technol., 102(17):8185-8190.

[55]Zhou, C., Lin, H., Ge, X., et al., 2015. The effects of dietary soybean isoflavones on growth, innate immune responses, hepatic antioxidant abilities and disease resistance of juvenile golden pompano Trachinotus ovatus. Fish Shellfish Immunol., 43(1):158-166.