Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom.
Nutraceutical Wellness, Inc. New York, NY, United States of America.
PLoS One. 2024 Feb 26;19(2):e0297080. doi: 10.1371/journal.pone.0297080. eCollection 2024.
Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/β.
Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17β-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERβ expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERβ and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry.
Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERβ ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERβ expression and a localization of ERs around the nuclear periphery.
As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERβ they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERβ is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERβ in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy.
在雌激素受体（ER）阳性乳腺癌治疗中，他莫昔芬会导致脱发/稀疏，这是一种常见的副作用。一些已知的促进头发生长的营养保健品在乳腺癌治疗期间被避免使用，因为担心它们具有植物雌激素活性。然而，并非所有植物成分都与雌激素相似，实际上，没有关于这些成分与他莫昔芬真正相互作用的信息。因此，这项研究旨在确定营养保健品（+/- 雌激素/他莫昔芬）对乳腺癌细胞增殖和 ERα/β 相对表达的影响。
在 17β-雌二醇和他莫昔芬存在或不存在的情况下，评估海带、虾青素、锯棕榈、生育三烯酚、玛卡、木贼、白藜芦醇、姜黄素和 Ashwagandha 对 MCF7、T47D 和 BT483 乳腺癌细胞系的增殖作用。在使用之前，通过高效液相色谱法（HPLC）分析每个提取物。通过 qRT-PCR 和 Western blot 评估细胞 ERα 和 ERβ 的表达。通过免疫细胞化学证实了与营养保健品孵育后 ERα：ERβ 的细胞内定位变化及其比值。
雌二醇刺激三种不同的乳腺癌细胞系（MCF7、T47D 和 BT483）的 DNA 合成，他莫昔芬抑制了这种作用；这与 T47D 和 BT483 细胞中的特定 ERa 激动剂相吻合。总的来说，营养保健品并没有干扰他莫昔芬对雌激素的抑制作用；有些甚至在与他莫昔芬联合使用时进一步诱导抑制作用。在所有细胞系中，ERα：ERβ 的比值在 mRNA 和蛋白质水平上都更高。然而，与营养保健品孵育诱导 ERβ 表达升高，并使 ER 定位于核周周围。
由于 ERα 是雌激素依赖性乳腺癌的关键驱动因素，如果营养保健品对 ERβ 具有更高的亲和力，它们可能提供保护作用，特别是如果它们协同作用并增强他莫昔芬的作用。由于 ERβ 是毛囊中的主要 ER，进一步的研究证实营养保健品是否能在毛囊细胞中使 ERβ 的比值向其倾斜，将支持它们在头发生长中的作用。尽管需要更多的研究来评估安全性和疗效，但这一有希望的数据表明，营养保健品作为接受内分泌治疗的乳腺癌患者脱发的辅助治疗具有潜力。
