Anticancer actions of Schizandra chinensis by Joseph J Collins, RN, ND

Schisandra chinensis has a number of active constituents that have documented anticancer actions including schisandrol A, schisandrol B, schizandrin, schisandrin b, schisantherin A, schizantherin C, α-iso-cubebenol, gomisin A, gomisin D, and gomisin G, gomisin N [1], [2], [3], [4], [5], [6], [7], [8], [9], [10].
Schizandrin has an antiproliferative effect that inhibited growth of cultured human breast cancer [11], [12],
Schizandrin B, one of the main ingredients in Schisandra chinensis inhibits the proliferation, triggers apopotosis, and inhibited the invasion and migration (metastasis) of lung cancer, which is the leading cause of cancer death in the world [13] schizantherin C also has antiproliferative effects on human lung cancer cells [14].
Gomisin G, gomisin N and α-iso-cubebenol from Schisandra chinensis have anti-tumor activities and is considered a candidate for anti-liver cancer therapy [15], [16], [17] , [18]. Of interest, Shizandrin B could be a therapeutic agent for prevention and treatment of non-alcoholic fatty-liver disease (NAFLD) [19], [20], [21].
Gomisin A induces apoptosis (programmed cell death) of colon cancer cells [22]. The whole extract of Schizandra chinensis has also demonstrated anticancer activity against colon cancer cells [23], [24], [25].
Schizandra chinensis extract might be an effective chemotherapeutic for the treatment of human gastric cancer (stomach cancer), the second most common cause of cancer-related death worldwide [26], [27].
Schisandra chinensis extract can prevent prostate and thyroid cancer [28], and may also help decrease symptoms of benign prostate hyperplasia [29].
Schizandra chinensis extract could serve as a new and promising adjuvant when used with chemotherapy drugs, such as 5- fluorouracil (5-Fu) [30]. Other studies noting the antitumor activities of Schizandra chinensis suggest that it may be an adjuvant against cancer when used with alternative and pharmaceutical therapies [31] by enhancing the effect of cancer drugs and reversing drug resistance [32],[33], [34], [35]

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References
To review the PubMed listing of any reference, go to www.ncbi.nlm.nih.gov/PubMed/ and enter the PubMed PMID number at the end of the reference.
1] Fong WF, Wan CK, Zhu GY, Chattopadhyay A, Dey S, Zhao Z, Shen XL. Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes. Planta Med. 2007 Mar;73(3):212-20. Epub 2007 Feb 22. PubMed PMID: 17318783.
[2] E Q, Tang M, Zhang X, Shi Y, Wang D, Gu Y, Li S, Liang X, Wang Z, Wang C. Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis against serum and glucose deprivation injury in SH-SY5Y cells. Cell Biol Int. 2015 Aug 20. doi: 10.1002/cbin.10537. [Epub ahead of print] PubMed PMID:
26289388.
[3] Li L, Pan Q, Sun M, Lu Q, Hu X. Dibenzocyclooctadiene lignans: a class of novel inhibitors of multidrug resistance-associated protein 1. Life Sci. 2007 Jan 30;80(8):741-8. Epub 2006 Nov 10. PubMed PMID: 17129588.
[4] Song JH, Cui L, An LB, Li WT, Fang ZZ, Zhang YY, Dong PP, Wu X, Wang LX, Gonzalez FJ, Sun XY, Zhao DW. Inhibition of UDP-Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis. Phytother Res. 2015 Jun 18. doi: 10.1002/ptr.5395. [Epub ahead of print] PubMed PMID: 26084208.
[5] Waiwut P, Shin MS, Yokoyama S, Saiki I, Sakurai H. Gomisin A enhances tumor necrosis factor-α-induced G1 cell cycle arrest via signal transducer and activator of transcription 1-mediated phosphorylation of retinoblastoma protein.Biol Pharm Bull. 2012;35(11):1997-2003. PubMed PMID: 23123471.
[6] Kim JE, Kim SG, Goo JS, Park da J, Lee YJ, Hwang IS, Lee HR, Choi SI, Lee YJ, Oh CH, Choi YW, Hwang DY. The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells. Oncol Rep. 2012 Sep;28(3):1103-9. doi: 10.3892/or.2012.1875. Epub 2012 Jun 19. PubMed PMID: 22736046.
[7] Inoue H, Waiwut P, Saiki I, Shimada Y, Sakurai H. Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5. Int J Oncol. 2012 Apr;40(4):1058-65. doi: 10.3892/ijo.2011.1299. Epub 2011 Dec 15. PubMed PMID: 22179661.
[8] Hwang D, Shin SY, Lee Y, Hyun J, Yong Y, Park JC, Lee YH, Lim Y. A compound isolated from Schisandra chinensis induces apoptosis. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6054-7. doi: 10.1016/j.bmcl.2011.08.065. Epub 2011 Aug 22. PubMed PMID: 21903389.
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[10] Min HY, Park EJ, Hong JY, Kang YJ, Kim SJ, Chung HJ, Woo ER, Hung TM, Youn UJ, Kim YS, Kang SS, Bae K, Lee SK. Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells. Bioorg Med Chem Lett. 2008 Jan 15;18(2):523-6. Epub 2007 Nov 28. PubMed PMID: 18063366.
[11] Kim SJ, Min HY, Lee EJ, Kim YS, Bae K, Kang SS, Lee SK. Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 2010 Feb;24(2):193-7. doi: 10.1002/ptr.2907. PubMed PMID: 19585470.
[12] Kim SJ, Min HY, Lee EJ, Kim YS, Bae K, Kang SS, Lee SK. Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 2010 Feb;24(2):193-7. doi: 10.1002/ptr.2907. PubMed PMID: 19585470.
[13] Lv XJ, Zhao LJ, Hao YQ, Su ZZ, Li JY, Du YW, Zhang J. Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis. Int J Clin Exp Med. 2015 May 15;8(5):6926-36. eCollection 2015. PubMed PMID: 26221229.
[14] Min HY, Park EJ, Hong JY, Kang YJ, Kim SJ, Chung HJ, Woo ER, Hung TM, Youn UJ, Kim YS, Kang SS, Bae K, Lee SK. Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells. Bioorg Med Chem Lett. 2008 Jan 15;18(2):523-6. Epub 2007 Nov 28. PubMed PMID: 18063366.
[15] Xiaoyang L, Chenming N, Chengqing L, Tao L. Drug-drug interation prediction between ketoconazole and anti-liver cancer drug Gomisin G. Afr Health Sci. 2015Jun;15(2):590-3. doi: 10.4314/ahs.v15i2.35. PubMed PMID: 26124807.
[16] Kim JE, Kim SG, Goo JS, Park da J, Lee YJ, Hwang IS, Lee HR, Choi SI, Lee YJ, Oh CH, Choi YW, Hwang DY. The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells. Oncol Rep. 2012 Sep;28(3):1103-9. doi: 10.3892/or.2012.1875. Epub 2012 Jun 19. PubMed PMID: 22736046.
[17] Kim SJ, Min HY, Lee EJ, Kim YS, Bae K, Kang SS, Lee SK. Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 2010 Feb;24(2):193-7. doi: 10.1002/ptr.2907. PubMed PMID: 19585470.
[18] Lee SB, Kim CY, Lee HJ, Yun JH, Nho CW. Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2. Planta Med. 2009 Oct;75(12):1314-8. doi: 10.1055/s-0029-1185685. Epub 2009 May 18. PubMed PMID: 19452436.
[19] Kwan HY, Niu X, Dai W, Tong T, Chao X, Su T, Chan CL, Lee KC, Fu X, Yi H, Yu H, Li T, Tse AK, Fong WF, Pan SY, Lu A, Yu ZL. Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers. Sci Rep. 2015 Mar 13;5:9114. doi: 10.1038/srep09114. PubMed PMID: 25766252.
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[21] Park HJ, Lee SJ, Song Y, Jang SH, Ko YG, Kang SN, Chung BY, Kim HD, Kim GS, Cho JH. Schisandra chinensis prevents alcohol-induced fatty liver disease in rats. J Med Food. 2014 Jan;17(1):103-10. doi: 10.1089/jmf.2013.2849. PubMed PMID: 24456360.
[22] Hwang D, Shin SY, Lee Y, Hyun J, Yong Y, Park JC, Lee YH, Lim Y. A compound isolated from Schisandra chinensis induces apoptosis. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6054-7. doi: 10.1016/j.bmcl.2011.08.065. Epub 2011 Aug 22. PubMed PMID: 21903389.
[23] Venkanna A, Siva B, Poornima B, Vadaparthi PR, Prasad KR, Reddy KA, Reddy GB,
Babu KS. Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity. Fitoterapia. 2014 Jun;95:102-8. doi: 10.1016/j.fitote.2014.03.003. Epub 2014 Mar 13. PubMed PMID: 24631765.
[24] Gnabre J, Unlu I, Chang TC, Lisseck P, Bourne B, Scolnik R, Jacobsen NE, Bates R, Huang RC. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 15;878(28):2693-700. doi: 10.1016/j.jchromb.2010.08.005. Epub 2010 Aug 14. PubMed PMID: 20810329.
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[26] Kim HS, Lee JH, Park HS, Lee GS, Kim HW, Ha KT, Kim BJ. Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway. Pharm Biol. 2015 Feb;53(2):212-9. doi: 10.3109/13880209.2014.913297. Epub 2014 Sep 22. PubMed PMID: 25243868.
[27] Chan AS, Yip EC, Yung LY, Pang H, Luk SC, Pang SF, Wong YH. Immuno-regulatory effects of CKBM on the activities of mitogen-activated protein kinases and the release of cytokines in THP-1 monocytic cells. Biol Pharm Bull. 2005 Sep;28(9):1645-50. PubMed PMID: 16141532.
[28] E Q, Tang M, Zhang X, Shi Y, Wang D, Gu Y, Li S, Liang X, Wang Z, Wang C. Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis against serum and glucose deprivation injury in SH-SY5Y cells. Cell Biol Int.2015 Aug 20. doi: 10.1002/cbin.10537. [Epub ahead of print] PubMed PMID: 26289388.
[29] Choo SH, Sung HH, Chae MR, Kang SJ, Han DH, Park JK, So I, Lee SW. Effects of Schisandra chinensis extract on the relaxation of isolated human prostate tissue and smooth muscle cell. J Ethnopharmacol. 2014 Oct 28;156:271-6. doi: 10.1016/j.jep.2014.08.025. Epub 2014 Aug 30. PubMed PMID: 25178950.
[30] Zhao T, Mao G, Zhang M, Zou Y, Feng W, Gu X, Zhu Y, Mao R, Yang L, Wu X. Enhanced antitumor and reduced toxicity effect of Schisanreae polysaccharide in 5-Fu treated Heps-bearing mice. Int J Biol Macromol. 2014 Feb;63:114-8. doi: 10.1016/j.ijbiomac.2013.10.037. Epub 2013 Nov 2. PubMed PMID: 24189396.
[31] Zhao T, Mao G, Mao R, Zou Y, Zheng D, Feng W, Ren Y, Wang W, Zheng W, Song J, Chen Y, Yang L, Wu X. Antitumor and immunomodulatory activity of a water-soluble low molecular weight polysaccharide from Schisandra chinensis (Turcz.) Baill. Food Chem Toxicol. 2013 May;55:609-16. doi: 10.1016/j.fct.2013.01.041. Epub 2013 Feb 12. PubMed PMID: 23416131.
[32] Fong WF, Wan CK, Zhu GY, Chattopadhyay A, Dey S, Zhao Z, Shen XL. Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes. Planta Med. 2007 Mar;73(3):212-20. Epub 2007 Feb 22. PubMed PMID: 17318783.
[33] Pan Q, Lu Q, Zhang K, Hu X. Dibenzocyclooctadiene lingnans: a class of novel inhibitors of P-glycoprotein. Cancer Chemother Pharmacol. 2006 Jul;58(1):99-106. Epub 2005 Oct 18. PubMed PMID: 16231181.
[34] Qiangrong P, Wang T, Lu Q, Hu X. Schisandrin B--a novel inhibitor of P-glycoprotein. Biochem Biophys Res Commun. 2005 Sep 23;335(2):406-11. PubMed PMID: 16084496.
[35] Li L, Pan Q, Sun M, Lu Q, Hu X. Dibenzocyclooctadiene lignans: a class of novel inhibitors of multidrug resistance-associated protein 1. Life Sci. 2007 Jan 30;80(8):741-8. Epub 2006 Nov 10. PubMed PMID: 17129588.