Drug Herb Interactions: Tamoxifen by M.M. Van Benschoten, OMD

Drug Herb Interactions: Tamoxifen by M.M. Van Benschoten, OMD

The primary clinical use of Tamoxifen is for prevention and treatment of estrogen receptor positive breast cancer. Tamoxifen acts as an antagonist, blocking the binding of estrogen to the receptor site, reducing DNA synthesis and cancer growth. The research literature contains many references to herbal medicines that interact with Tamoxifen by enhancement or inhibition of antitumor effects. Tamoxifen is metabolized by the liver into the active metabolite, 4-hydroxytamoxifen. This transformation is induced by cytochrome P450 CYP2D6 and CYP3A4 enzymes. Herbs interacting with these liver enzymes may reduce clinical effectiveness of the drug.

CYP2D6 inhibit
alpinia officinarum (gao liang jiang), epimedium (yin yang huo), ginkgo leaf (yin xing ye), piper nigrum (hu jiao), punica granatum (shi liu pi), rhodiola (hong jing tian)

CYP3A4 inhibit
andrographis (chuan xin lian), agaricus (ji song rong), bamboo (zhu ru), camellia (lu cha), cimicifuga (sheng ma), curcuma longa (jiang huang), curcuma zedoria (e zhu), epimedium (yin yang huo), evodia (wu chu yu), fennel (xiao hui xiang), ginger (sheng jiang), ginseng (ren shen), grape seed (pu tao zi), licorice (gan cao), rhodiola (hong jing tian), schizandra (wu wei zi), valerian (jie cao)

All the above species are contraindicated in patients taking Tamoxifen, as they can inhibit the transformation of the drug to its bioactive state. Cancer patients often self prescribe curcumin/tumeric and mushroom preparations based on their anticancer effects without considering interactions with prescription medications.

Tamoxifen enhance
camellia (lu cha), cimicifuga (sheng ma), linum (flax seed), morus branch (sang zhi), silybum (shui fei ji)

These species can increase bioavailability of Tamoxifen, and inhibit growth of Tamoxifen resistant cancer cells. Camellia and cimicifuga are CYP3A4 inhibitors, so their use should be avoided.

Tamoxifen inhibit
citrus peel (chen pi), coptis (huang lian), curcuma longa (jiang huang), sesame (hu ma ren)
siwutang (angelica sinensis/dang gui, rehmannia/di huang, cnidium/chuan xiong, paeony/bai shao)

The above list of species has been demonstrated to specifically inhibit the antitumor effect of Tamoxifen.
Angelica sinensis/dang gui, cnidium/chuan xiong, and paeony/bai shao also increase progesterone, which makes them contraindicated in PR+ progesterone receptor positive breast cancer.

References

Integr Cancer Ther. 2014 Feb 12;13(3):226-239. [Epub ahead of print]
In Vitro and In Vivo Effects of Jia-Wei-Xiao-Yao-San in Human Breast Cancer MCF-7 Cells Treated With Tamoxifen. Chen JL1, Chang CJ2, Wang JY3, Wen CS4, Tseng LM5, Chang WC6, Noomhorm N6, Liu HJ6, Chen WS3, Chiu JH7, Shyr YM3.

Menopause. 2013 Jun;20(6):646-54. doi: 10.1097/gme.0b013e31827b2240.
In vivo and in vitro demonstration of herb-drug interference in human breast cancer cells treated with tamoxifen and trastuzumab. Chen JL1, Wang JY, Tsai YF, Lin YH, Tseng LM, Chang WC, King KL, Chen WS, Chiu JH, Shyr YM.

Anticancer Res. 2010 Jan;30(1):79-85.
Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Kim CS, Choi SJ, Park CY, Li C, Choi JS. College of Pharmacy, Chosun University, Dong-Gu, Gwangju 501-759, Republic of Korea.

J Natl Cancer Inst. 1999 Feb 17;91(4):354-9.
Influence of tangeretin on tamoxifen's therapeutic benefit in mammary cancer.
Bracke ME, Depypere HT, Boterberg T, Van Marck VL, Vennekens KM, Vanluchene E,
Nuytinck M, Serreyn R, Mareel MM. Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, University Hospital, Gent, Belgium. marc1.bracke@rug.ac.be [1]

Indian J Exp Biol. 2010 Mar;48(3):280-8.
Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin. El-Beshbishy HA, Mohamadin AM, Nagy AA, Abdel-Naim AB.
Medical Laboratories Technology Dept., Facuty of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. hesham_elbeshbishy@hotmail.com [2]

Food Chem Toxicol. 2010 Nov;48(11):3227-34. Epub 2010 Sep 4.
Inhibition of angiogenesis by quercetin in tamoxifen-resistant breast cancer cells.Oh SJ, Kim O, Lee JS, Kim JA, Kim MR, Choi HS, Shim JH, Kang KW, Kim YC. College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

Biosci Rep. 2011 Apr;31(2):99-108.
(-)-Epigallocatechin-3-gallate down-regulates EGFR, MMP-2, MMP-9 and EMMPRIN and
inhibits the invasion of MCF-7 tamoxifen-resistant cells. vFarabegoli F, Papi A, Orlandi M.
Department of Experimental Pathology, University of Bologna, Bologna, Italy. fulvia.farabegoli@unibo.it [3]

Clin Cancer Res. 2004 Nov 15;10(22):7703-11.
Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice. Chen J(1), Hui E, Ip T, Thompson LU. (1)Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.

Can J Physiol Pharmacol. 2007 Nov;85(11):1153-9.
Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Al-Akoum M1, Dodin S, Akoum A.

Cancer. 1999 May 1;85(9):1937-42.
Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Lin HL1, Liu TY, Lui WY, Chi CW.

Exp Biol Med (Maywood). 2007 Jun;232(6):754-61.
Interaction of sesame seed and tamoxifen on tumor growth and bone health in athymic mice.
Sacco SM1, Power KA, Chen J, Ward WE, Thompson LU.

Menopause. 2005 Nov-Dec;12(6):734-40. Epub 2005 Nov 8.
Use of dong quai (Angelica sinensis) to treat peri- or postmenopausal symptoms in women with breast cancer: is it appropriate? Lau CB1, Ho TC, Chan TW, Kim SC.

In Vivo. 2008 May-Jun;22(3):391-5.
Effects of morin on the bioavailability of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats.
Shin SC, Piao YJ, Choi JS. College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea

Lakartidningen. 2005 Oct 31-Nov 6;102(44):3226-8, 3230-1.
[Natural remedies and hormone preparations--potential risk for breast cancer patients. A study surveys the use of agents which possibly counteract with the treatment] [Article in Swedish] Malekzadeh F, Rose C, Ingvar C, Jernström H.