The use of curcumin in breast cancer

Breast cancer is the primary cause of cancer mortality in women and represents a serious public health problem worldwide. Thanks to the development of technology, earlier diagnosis has been made possible, but the death rate from this malignant disease is still high. Currently available treatment options include surgery, radiotherapy, adjuvant chemotherapy and hormone therapy. However, an effective cure for advanced breast cancer has not yet been found.

Recent research has revealed new approaches to treatment. One of such approaches is chemoprevention, which is the use of natural or synthetic substances with the aim of preventing, slowing down and suppressing the process of carcinogenesis. Curcumin is a polyphenolic compound that comes from the root of turmeric (lat. Curcuma longa), and is responsible for the specific yellow color of this plant.

Current research shows that curcumin has anti-inflammatory and anticarcinogenic properties. In addition, it significantly inhibits cancer growth, reduces the possibility of metastasis and is considered an effective chemotherapeutic and chemopreventive agent (1).

Scientific research: curcumin and breast cancer

Curcumin and radiotherapy
Radiation dermatitis affects approximately 95% of women with breast cancer who receive radiation therapy. In one clinical study, 30 women with breast cancer with an average age of 58.1 years participated who, during the radiotherapy period, simultaneously received curcumin in the form of a dietary supplement in a dose of 6.0 grams (3 times a day, 2.0 grams of curcumin) or a placebo.The results showed that in those subjects who took curcumin, compared to the subjects who received a placebo, a reduction in the severity of the symptoms of radiation dermatitis was observed (2).

Curcumin and chemotherapy

Doxorubicin je antibiotik iz skupine antraciklina koji se uobičajeno koristi kao kemoterapeutik u liječenju različitih vrsta karcinoma, uključujući i karcinom dojke. Istraživanja pokazuju da terapija doksorubicinom, u kombinaciji s kurkuminom, ima značajno veću učinkovitost u senzibilizaciji karcinogenih stanica koje su otporne na doksorubicin, kao i na smanjenje preživljenja spomenutih karcinogenih stanica. Osim toga, pokazalo se da kurkumin potiče imuno-, hepato- i kardioprotektivna svojstva doksorubicina (3).
Cisplatin je anorganska tvar s antineoplastičnim svojstvima, široko rasprostranjena u liječenju tumorskih tvorevina, uključujući i karcinom dojke. Međutim, korištenje ovog lijeka je ograničeno zbog njegove dokazane nefrotoksičnosti. Cilj istraživanja objavljenog u časopisu Frontiers in Pharmacology was to determine the effect of the combination of cisplatin and curcumin in the treatment of induced mammary carcinoma in female rats. The results showed that taking curcumin alleviated the nephrotoxicity of cisplatin and improved its anticarcinogenic activity (4).
In a controlled study, the aim of which was to examine the effect of taking a dietary supplement with curcumin (a total of 300 mg of curcuminoids) on alleviating the symptoms of chemotherapy and radiotherapy, 160 people suffering from various types of cancer who underwent the mentioned therapies participated. In subjects who received curcumin, compared to the control group, a reduction in the side effects of chemotherapy and radiation, such as nausea, vomiting, diarrhea, constipation and weight loss, was observed (5).

Mechanism of action

The anticarcinogenic effect of curcumin is manifested in the influence on the proliferation and apoptosis of cancerous cells, their cell cycle, and in reducing the possibility of metastasis and angiogenesis.

• Signalne molekule koje stanicama karcinoma dojke omogućuju preživljenje, poput NF-κB imaju središnju ulogu u proliferaciji karcinogenih stanica. Dokazano je da kurkumin može inhibirati ekspresiju NF-κB i utjecati na mnoge signalne puteve što posljedično utječe na smanjenje djelovanja upalnih citokina, kao što su CXCL1 i CXCL2, te ekspresiju matriks metaloproteinaze – 9 (MMP-9), urokinaznog plazminogen aktivatora (uPA), uPA receptora (uPAR), unutarstanične adhezijske molekule – 1 (ICAM-1) i kemokinskog receptora 4. Zbog toga se vjeruje kako kurkumin ima utjecaj na rast i invaziju karcinogenih stanica dojke (7,8,9).

Apoptosis
Istraživanja pokazuju kako kurkumin može inducirati apoptozu karcinogenih stanica dojke na način da utječe na regulaciju ekspresije gena i proteina uključenih u proces apoptoze – omogućava ekspresiju HIAP1, CRAF1, GADD45, HPRT, MCL-1, BCL2L2, NIP1, TRAP3, GSTP1, PIG11, DAXX, PIG3, RBP2 i JNK1 gena i Bax proteina te sprječava ekspresiju TRAIL, AP13, TNFR, SARP3, TRAIL-R2, TNFRSF5, TNFb i hTRIP gena i Bcl2 proteina (10).

Cell cycle arrest

Curcumin can also affect carcinogenic breast cells by promoting cell cycle arrest in G2M and late S phase of the cell cycle in MCF-7 estrogen-dependent cells (11).

Inhibition of cancer growth

Curcumin suppresses the growth of breast cancer through an indirect effect on the immune system. Namely, recent research has shown that curcumin could prevent the decrease in the number of T-cells and affects the action of immuno-suppressive cytokines, including transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). Curcumin can also suppress the growth of breast cancer by acting on metastatic factors in two ways. The first way is by inhibiting angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in ER-negative breast cancer cells. Another mode of action of curcumin is through its influence on the expression of adhesion molecules (such as integrin α6β4) and on matrix metalloproteinase-9 and intracellular adhesion molecule 1 (6).

Conclusion

The therapeutic effect of curcumin in the treatment of numerous diseases has been the center of interest of scientists for many years.

Due to its proven anti-inflammatory and anticarcinogenic effects and its effect on increasing the effect of chemotherapeutics, as well as reducing the side effects of standard therapy, curcumin is an aid in the treatment of breast cancer.

Author: Tena Škunca, M.Sc. / Vitaminoteka

Literature:

1. Ko, EY, Moon A. Natural Products for Chemoprevention of Breast Cancer. J Cancer Prev 2015; 10(4):223-231.

2. Ryana, JL, Hecklerb, CE, Lingb, M, Katzb, A, Williams, JP, Pentlanda, AP, Morrow, GR. Curcumin for Radiation Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Thirty Breast Cancer Patients. Radiat Res 2013; 180(1): 34–43.

3. Panda, AK, Chakraborty, D, Sarkar, I, Khan, T, Sa, G.New insights into therapeutic activity and anticancer properties of curcumin. J Exp Pharmacol 2017; 9:31-45.

4. Kumar, P, Barua, CC, Sulakhiya, K, Sharma, RK. Curcumin Ameliorates Cisplatin-Induced Nephrotoxicity and Potentiates Its Anticancer Activity in SD Rats: Potential Role of Curcumin in Breast Cancer Chemotherapy. Front Pharmacol 2017; 8:132. doi: 10.3389/fphar.2017.00132

5. Belcaro G, Hosoi M, Pellegrini L, Appendino G, Ippolito E, Ricci A, Ledda A, Dugall M, Cesarone MR, Maione C, Ciammaichella G, Genovesi D, Togni S. A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment. Phytother Res 2014 28(3):444-50. doi: 10.1002/ptr.5014.

6. Wang, Y, Yu, J, Cui, R, Lin, J, Ding, X. Curcumin in Treating Breast Cancer: A Review. J Lab Autom 2016;21(6):723-731

7. Liu, Q, Loo, WTY, Sze, SCW et al. Curcumin Inhibits Cell Proliferation of MDA-MB-231 and BT-483 Breast Cancer Cells Mediated by Down-Regulation of NFκB, CyclinD and MMP-1 Transcription. Phytomedicine 2009; 16(10):916-922.

8. Bachmeier, BE, Mohrenz, IV, Mirisola, V et al. Curcumin Downregulates the Inflammatory Cytokines CXCL1 and -2 in Breast Cancer Cells via NFκB. Carcinogenesis 2008; 29(4):779–789.

9. Yodkeeree, S, Ampasavate, C, Sung, B et al. Demethoxycurcumin Suppresses Migration and Invasion of MDA-MB-231 Human Breast Cancer Cell Line. Eur J Pharmacol 2010;627 (1):8–15.

10. Lv, ZD, Liu, XP, Zhao, WJ et al. Curcumin Induces Apoptosis in Breast Cancer Cells and Inhibits Tumor Growth In Vitro and In Vivo. Int J Clin Exp Pathol 2014;7(6):2818.

11. Ramachandran, C, Fonseca, HB, Jhabvala, P et al.Curcumin Inhibits Telomerase Activity through Human Telomerase Reverse Transcriptase in MCF-7 Breast Cancer Cell Line. Cancer Lett 2002; 184(1):1–6.

12. Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 2014;58(3):516-27.