Anticancer actions of Cimicifuga racemosa (Black Cohosh) by Joseph J Collins, RN, ND

Cimicifuga racemosa (black cohosh) extracts have been proposed as a safe non-hormonal treatment alternative for patients with a history of breast cancer [1], [2], and are recognized as having no estrogenic effects on the breasts [3], [4]. Extracts of black cohosh do not bind to estrogen receptors and have no estrogenic effect on breast tissue or uterine tissue [5], supporting the concept of black cohosh extracts being a safe substitute for HRT. In fact, black cohosh has also been recognized as safe for women with uterine fibroids [6] 

Black cohosh is considered to be safe in breast cancer patients as an inhibitor of tumor growth [7].

Black cohosh may have a chemopreventive potential for mammary cancer [8]. The Black cohosh extract have been shown to specifically suppress expression of human breast cancer (MCF-7) cells [9] and cause apoptosis of the breast cancer cells [10]. 

While antiproliferative and proapoptotic actions was noted, there was no estrogenic effect on MCF-7 cells [11]. Research with MDA-MB-453 human breast cancer cells also suggest that black cohosh extract may be useful in the prevention and therapy of breast cancer [12].

Actein from the herb black cohosh preferentially inhibits the growth of breast cancer cells [13]. Actein induced apoptosis in human breast cancer cells, suggest that compounds from Cimicifuga species may be useful in the prevention and treatment of human breast cancer [14]. Other compounds in black cohosh also showed cytotoxic activity against cancer cells [15], [16].

Black cohosh may also cause apoptosis of gastric cancer cells [17] and may potentially find use as a new therapy for the treatment of hepatoma [18], [19]

Black cohosh extract seems to be a reasonable adjuvant treatment in combination with tamoxifen treated breast cancer patients [20] due to synergistic cytotoxic effects for when used with tamoxifen for inhibition of cancerous cell growth [21]. Adding black cohosh extract to tamoxifen therapy also decreases the risk of breast cancer recurrence [22]. Black cohosh has also been used as an adjuvant with the aromatase inhibitor formestane [23]. Black cohosh extracts may also increase the effectiveness of other anticancer agents [24], [25]

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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] Drewe J, Bucher KA, Zahner C. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. Springerplus. 2015 Feb 10;4:65. doi: 10.1186/s40064-015-0808-y. eCollection 2015. PubMed PMID: 25713759.

[2] Roberts H. Safety of herbal medicinal products in women with breast cancer. Maturitas. 2010 Aug;66(4):363-9. doi: 10.1016/j.maturitas.2010.02.010. Epub 2010 Mar 27. Review. PubMed PMID: 20347238.

[3] Seidlova-Wuttke D, Jarry H, Wuttke W. Plant derived alternatives for hormone replacement therapy (HRT). Horm Mol Biol Clin Investig. 2013 Dec;16(1):35-45. doi: 10.1515/hmbci-2013-0024. PubMed PMID: 25436745.

[4] Ruhlen RL, Haubner J, Tracy JK, Zhu W, Ehya H, Lamberson WR, Rottinghaus GE, Sauter ER. Black cohosh does not exert an estrogenic effect on the breast. Nutr Cancer. 2007;59(2):269-77. PubMed PMID: 18001221.

[5] Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol. 2014 Jan;139:302-10. doi: 10.1016/j.jsbmb.2013.02.007. Epub 2013 Feb 28. Review. PubMed PMID: 23459142.

[6] Ross SM. Efficacy of a standardized isopropanolic black cohosh (Actaea racemosa) extract in treatment of uterine fibroids in comparison with tibolone among patients with menopausal symptoms. Holist Nurs Pract. 2014 Nov-Dec;28(6):386-91. doi: 10.1097/HNP.0000000000000055. Review. PubMed PMID: 25314113.

[7] Walji R, Boon H, Guns E, Oneschuk D, Younus J. Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients. Support Care Cancer. 2007 Aug;15(8):913-21. Epub 2007 Jun 30. Review. PubMed PMID: 17602247.

[8] Einbond LS, Soffritti M, Degli Esposti D, Tibaldi E, Lauriola M, Bua L, He K, Genovese G, Su T, Huggins L, Wang X, Roller M, Wu HA. Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats. Anticancer Res. 2012 Jan;32(1):21-30. PubMed PMID: 22213284.

[9] Soler MC, Molina JL, Díaz HA, Pinto VC, Barrios YL, He K, Roller M, Weinstein-Oppenheimer CR. Effect of the standardized Cimicifuga foetida extract on Hsp 27 expression in the MCF-7 cell line. Biol Res. 2011;44(3):243-9. doi: /S0716-97602011000300005. Epub 2011 Nov 7. PubMed PMID: 22688911.

[10] Fang ZZ, Nian Y, Li W, Wu JJ, Ge GB, Dong PP, Zhang YY, Qiu MH, Liu L, Yang L. Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway. Phytother Res. 2011 Jan;25(1):17-24. doi: 10.1002/ptr.3222. PubMed PMID: 20564500.

[11] Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M. Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7. BMC Pharmacol. 2007 Sep 20;7:11. PubMed PMID: 17880733; PubMed Central PMCID: PMC2194763.

[12] Einbond LS, Su T, Wu HA, Friedman R, Wang X, Jiang B, Hagan T, Kennelly EJ, Kronenberg F, Weinstein IB. Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth. Anticancer Res. 2007 Mar-Apr;27(2):697-712. PubMed PMID: 17465192.

[13] Einbond LS, Mighty J, Redenti S, Wu HA. Actein induces calcium release in human breast cancer cells. Fitoterapia. 2013 Dec;91:28-38. doi: 10.1016/j.fitote.2013.07.025. Epub 2013 Aug 9. PubMed PMID: 23939423.

[14] Einbond LS, Wen-Cai Y, He K, Wu HA, Cruz E, Roller M, Kronenberg F. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. 2008 Jun;15(6-7):504-11. Epub 2007 Nov 5.PubMed PMID: 17980565.

[15] Yim SH, Kim HJ, Park SH, Kim J, Williams DR, Jung DW, Lee IS. Cytotoxic caffeic acid derivatives from the rhizomes of Cimicifuga heracleifolia. Arch Pharm Res. 2012 Sep;35(9):1559-65. doi: 10.1007/s12272-012-0906-0. Epub 2012 Oct 9. PubMed PMID: 23054712.

[16] Lu L, Chen JC, Li Y, Qing C, Wang YY, Nian Y, Qiu MH. Studies on the constituents of Cimicifuga foetida collected in Guizhou Province and their cytotoxic activities. Chem Pharm Bull (Tokyo). 2012;60(5):571-7. PubMed PMID: 22689393.

[17] Guo LY, Joo EJ, Son KH, Jeon SJ, Jang S, Shin EM, Zhou HY, Kim YS. Cimiside E arrests cell cycle and induces cell apoptosis in gastric cancer cells. Arch Pharm Res. 2009 Oct;32(10):1385-92. doi: 10.1007/s12272-009-2007-2. Epub 2009 Nov 8. PubMed PMID: 19898801.

[18] Tian Z, Si J, Chang Q, Zhou L, Chen S, Xiao P, Wu E. Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma. BMC Cancer. 2007 Dec 31;7:237. doi: 10.1186/1471-2407-7-237. PubMed PMID: 18166137.

[19] Tian Z, Pan R, Chang Q, Si J, Xiao P, Wu E. Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis. J Ethnopharmacol. 2007 Nov 1;114(2):227-33. Epub 2007 Aug 12. PubMed PMID: 17881166.

[20] Rostock M, Fischer J, Mumm A, Stammwitz U, Saller R, Bartsch HH. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study. Gynecol Endocrinol. 2011 Oct;27(10):844-8. doi: 10.3109/09513590.2010.538097. Epub 2011 Jan 13. PubMed PMID: 21231853.

[21] Al-Akoum M, Dodin S, Akoum A. Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Can J Physiol Pharmacol. 2007 Nov;85(11):1153-9. PubMed PMID: 18066117.

[22] Henneicke-von Zepelin HH, Meden H, Kostev K, Schröder-Bernhardi D, Stammwitz U, Becher H. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther. 2007 Mar;45(3):143-54. PubMed PMID: 17416109.

[23] Nisslein T, Freudenstein J. Coadministration of the aromatase inhibitor formestane and an isopropanolic extract of black cohosh in a rat model of chemically induced mammary carcinoma. Planta Med. 2007 Apr;73(4):318-22. Epub 2007 Mar 12. PubMed PMID: 17354167.

[24] Liu DL, Li YJ, Yao N, Xu J, Chen ZS, Yiu A, Zhang CX, Ye WC, Zhang DM. Acerinol, a cyclolanstane triterpenoid from Cimicifuga acerina, reverses ABCB1-mediated multidrug resistance in HepG2/ADM and MCF-7/ADR cells. Eur J Pharmacol. 2014 Jun 15;733:34-44. doi: 10.1016/j.ejphar.2014.03.043. Epub 2014 Apr 4. PubMed PMID: 24704556.

[25] Dueregger A, Guggenberger F, Barthelmes J, Stecher G, Schuh M, Intelmann D, Abel G, Haunschild J, Klocker H, Ramoner R, Sampson N. Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055. Phytomedicine. 2013 Nov 15;20(14):1306-14. doi: 10.1016/j.phymed.2013.07.009. Epub 2013 Aug 23. PubMed PMID: 23972793.

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] Drewe J, Bucher KA, Zahner C. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. Springerplus. 2015 Feb 10;4:65. doi: 10.1186/s40064-015-0808-y. eCollection 2015. PubMed PMID: 25713759.

[2] Roberts H. Safety of herbal medicinal products in women with breast cancer. Maturitas. 2010 Aug;66(4):363-9. doi: 10.1016/j.maturitas.2010.02.010. Epub 2010 Mar 27. Review. PubMed PMID: 20347238.

[3] Seidlova-Wuttke D, Jarry H, Wuttke W. Plant derived alternatives for hormone replacement therapy (HRT). Horm Mol Biol Clin Investig. 2013 Dec;16(1):35-45. doi: 10.1515/hmbci-2013-0024. PubMed PMID: 25436745.

[4] Ruhlen RL, Haubner J, Tracy JK, Zhu W, Ehya H, Lamberson WR, Rottinghaus GE, Sauter ER. Black cohosh does not exert an estrogenic effect on the breast. Nutr Cancer. 2007;59(2):269-77. PubMed PMID: 18001221.

[5] Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol. 2014 Jan;139:302-10. doi: 10.1016/j.jsbmb.2013.02.007. Epub 2013 Feb 28. Review. PubMed PMID: 23459142.

[6] Ross SM. Efficacy of a standardized isopropanolic black cohosh (Actaea racemosa) extract in treatment of uterine fibroids in comparison with tibolone among patients with menopausal symptoms. Holist Nurs Pract. 2014 Nov-Dec;28(6):386-91. doi: 10.1097/HNP.0000000000000055. Review. PubMed PMID: 25314113.

[7] Walji R, Boon H, Guns E, Oneschuk D, Younus J. Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients. Support Care Cancer. 2007 Aug;15(8):913-21. Epub 2007 Jun 30. Review. PubMed PMID: 17602247.

[8] Einbond LS, Soffritti M, Degli Esposti D, Tibaldi E, Lauriola M, Bua L, He K, Genovese G, Su T, Huggins L, Wang X, Roller M, Wu HA. Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats. Anticancer Res. 2012 Jan;32(1):21-30. PubMed PMID: 22213284.

[9] Soler MC, Molina JL, Díaz HA, Pinto VC, Barrios YL, He K, Roller M, Weinstein-Oppenheimer CR. Effect of the standardized Cimicifuga foetida extract on Hsp 27 expression in the MCF-7 cell line. Biol Res. 2011;44(3):243-9. doi: /S0716-97602011000300005. Epub 2011 Nov 7. PubMed PMID: 22688911.

[10] Fang ZZ, Nian Y, Li W, Wu JJ, Ge GB, Dong PP, Zhang YY, Qiu MH, Liu L, Yang L. Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway. Phytother Res. 2011 Jan;25(1):17-24. doi: 10.1002/ptr.3222. PubMed PMID: 20564500.

[11] Gaube F, Wolfl S, Pusch L, Kroll TC, Hamburger M. Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7. BMC Pharmacol. 2007 Sep 20;7:11. PubMed PMID: 17880733; PubMed Central PMCID: PMC2194763.

[12] Einbond LS, Su T, Wu HA, Friedman R, Wang X, Jiang B, Hagan T, Kennelly EJ, Kronenberg F, Weinstein IB. Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth. Anticancer Res. 2007 Mar-Apr;27(2):697-712. PubMed PMID: 17465192.

[13] Einbond LS, Mighty J, Redenti S, Wu HA. Actein induces calcium release in human breast cancer cells. Fitoterapia. 2013 Dec;91:28-38. doi: 10.1016/j.fitote.2013.07.025. Epub 2013 Aug 9. PubMed PMID: 23939423.

[14] Einbond LS, Wen-Cai Y, He K, Wu HA, Cruz E, Roller M, Kronenberg F. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. 2008 Jun;15(6-7):504-11. Epub 2007 Nov 5.PubMed PMID: 17980565.

[15] Yim SH, Kim HJ, Park SH, Kim J, Williams DR, Jung DW, Lee IS. Cytotoxic caffeic acid derivatives from the rhizomes of Cimicifuga heracleifolia. Arch Pharm Res. 2012 Sep;35(9):1559-65. doi: 10.1007/s12272-012-0906-0. Epub 2012 Oct 9. PubMed PMID: 23054712.

[16] Lu L, Chen JC, Li Y, Qing C, Wang YY, Nian Y, Qiu MH. Studies on the constituents of Cimicifuga foetida collected in Guizhou Province and their cytotoxic activities. Chem Pharm Bull (Tokyo). 2012;60(5):571-7. PubMed PMID: 22689393.

[17] Guo LY, Joo EJ, Son KH, Jeon SJ, Jang S, Shin EM, Zhou HY, Kim YS. Cimiside E arrests cell cycle and induces cell apoptosis in gastric cancer cells. Arch Pharm Res. 2009 Oct;32(10):1385-92. doi: 10.1007/s12272-009-2007-2. Epub 2009 Nov 8. PubMed PMID: 19898801.

[18] Tian Z, Si J, Chang Q, Zhou L, Chen S, Xiao P, Wu E. Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma. BMC Cancer. 2007 Dec 31;7:237. doi: 10.1186/1471-2407-7-237. PubMed PMID: 18166137.

​[19] Tian Z, Pan R, Chang Q, Si J, Xiao P, Wu E. Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis. J Ethnopharmacol. 2007 Nov 1;114(2):227-33. Epub 2007 Aug 12. PubMed PMID: 17881166.

[20] Rostock M, Fischer J, Mumm A, Stammwitz U, Saller R, Bartsch HH. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study. Gynecol Endocrinol. 2011 Oct;27(10):844-8. doi: 10.3109/09513590.2010.538097. Epub 2011 Jan 13. PubMed PMID: 21231853.

[21] Al-Akoum M, Dodin S, Akoum A. Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Can J Physiol Pharmacol. 2007 Nov;85(11):1153-9. PubMed PMID: 18066117.

[22] Henneicke-von Zepelin HH, Meden H, Kostev K, Schröder-Bernhardi D, Stammwitz U, Becher H. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther. 2007 Mar;45(3):143-54. PubMed PMID: 17416109.

[23] Nisslein T, Freudenstein J. Coadministration of the aromatase inhibitor formestane and an isopropanolic extract of black cohosh in a rat model of chemically induced mammary carcinoma. Planta Med. 2007 Apr;73(4):318-22. Epub 2007 Mar 12. PubMed PMID: 17354167.

[24] Liu DL, Li YJ, Yao N, Xu J, Chen ZS, Yiu A, Zhang CX, Ye WC, Zhang DM. Acerinol, a cyclolanstane triterpenoid from Cimicifuga acerina, reverses ABCB1-mediated multidrug resistance in HepG2/ADM and MCF-7/ADR cells. Eur J Pharmacol. 2014 Jun 15;733:34-44. doi: 10.1016/j.ejphar.2014.03.043. Epub 2014 Apr 4. PubMed PMID: 24704556.

[25] Dueregger A, Guggenberger F, Barthelmes J, Stecher G, Schuh M, Intelmann D, Abel G, Haunschild J, Klocker H, Ramoner R, Sampson N. Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055. Phytomedicine. 2013 Nov 15;20(14):1306-14. doi: 10.1016/j.phymed.2013.07.009. Epub 2013 Aug 23. PubMed PMID: 23972793.