Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

3.7. Curcuma longa

Turmeric plant (Curcuma longa) is widely used in food as a dietary spice and in traditional medicine as a remedy for different diseases including diabetes and hepatic disturbances [291]. Curcumin, the active compound of turmeric, has antioxidant effects and has been demonstrated to be a promising agent in clinical oncology due to its chemopreventive, antiproliferative, and apoptosis effects [292].

Curcumin can modulate multiple biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, angiogenesis, tumour genesis, and metastasis, which could justify its anticancer outcome [293].

Various preclinical studies focused on the anticancer efficacy of curcumin have been tested in some cancer models including breast cancer. The inhibition effect of curcumin alone, in combination with chemotherapeutic agents, on in vitro human breast cancer cells lines has been proved [294–299]. The same effects have also been observed in animal models. Zhan and collaborators [296] demonstrated the increased antitumour efficacy on mouse models of combining paclitaxel with curcumin and suggested the promising therapeutic potential and underlying mechanisms of this therapeutic association in breast cancer treatment. Ferreira et al. reported the effectiveness in reducing tumour growth and cell proliferation as well as in the suppression of angiogenesis using intraperitoneally curcumin administration in a xenograft model of breast cancer [300]. Research studies referred to different molecular mechanisms underlying the antitumour activity of curcumin in breast cancer cells, such as modulating the NF-ƙB signalling pathway [296, 297, 301–303], decreasing HER2 oncoprotein expression, the phosphorylation of Akt, MAPK, the expression of NF-ƙB in both BT-474 and SK-BR-3-HR cell (i.e., a herceptin resistant strain from SK-BR-3) [304], and the induced apoptosis by inhibiting fatty acid synthase [305]. Additionally, some authors found that curcumin suppressed breast tumour angiogenesis through abrogating osteopontin or medroxyprogesterone acetate induced VEGF expression [306, 307]. Soung and Chung showed that the association of epigallocatechin gallate and curcumin has an efficacy outcome in both in vitro and in vivo models of ERα-breast cancer by the regulation of epidermal growth factor receptor expression [308].

Curcumin is a lipid-soluble compound with limited bioavailability and extensive metabolization. Some researchers used different technological strategies to sustain the delivery of curcumin and overcome the intrinsically poor bioavailability, such as nanotechnology and liposomal-based formulations and synthetic analogues of curcumin [309–313]. The results from these studies demonstrated promising outcomes for clinical transposition.

Most of the clinical trials that evaluated the curcumin used in cancer treatment refer to colorectal and pancreatic cancers. Bayet-Robert et al. [64] performed a clinical phase I dose escalation trial of combination docetaxel chemotherapy with curcumin in advanced and metastatic breast cancer patients. The authors confirmed the safety profile of this combination therapy which was consistent with that observed with a monotherapy of docetaxel. Additionally, curcumin/docetaxel combination proved antitumour activity and a superior response rate in comparison to docetaxel in monotherapy. The recommended dose of curcumin is 6.0 g/day for seven consecutive days every 3 weeks in combination with a standard dose of docetaxel which proved its feasibility, safety, and tolerability. However, some scientific evidence demonstrated that dietary curcumin can inhibit chemotherapy-induced apoptosis in models of human breast cancer lines (MCF-7, MDA-MB-231, and BT-474) [314]. The chemotherapeutic agents evaluated were camptothecin, mechlorethamine, and doxorubicin-induced apoptosis. In conclusion, additional clinical studies are required to demonstrate the avoidance of curcumin (in both supplements and intake foods containing curcuma) in breast cancer patients undergoing chemotherapy.

In addition, this phytotherapeutic agent is well tolerated in human subjects. Therefore, curcumin could be considered an alternative nontoxic agent in the treatment of one of the most aggressive breast cancer, that is, triple negative breast cancer (ER-negative, PR-negative, and HER2/neu not over expressed) [303]. This breast cancer remains the most challenging factor in cancer treatment.