Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062 India.
Department of Pharmacy, National University of Singapore, Singapore 117559, Singapore.
Med Hypotheses. 2019 Nov;132:109379. doi: 10.1016/j.mehy.2019.109379. Epub 2019 Aug 22.
Breast cancer is second most leading cause of death in all over the world and not only limited to the females. Tamoxifen has been considered as the gold line therapy for estrogen receptor positive breast cancer. However, this chemopreventive approach has been focused at individuals in high risk group and limits its clinical applications to moderate and/or lower risk groups. Moreover, Tamoxifen treatment is associated with a dose related hepatotoxicity and nephrotoxicity and eventually results in poor quality of life of patients. Sulphoraphane, a naturally occurring isothiocyanate derivative has been investigated for its numerous potential biological activities including anticancer effects. The present hypothesis aims to put forward in which Tamoxifen is combined with a natural bioactive Sulphoraphane, both incorporated into a novel lipid based nanocarrier at a reduced dose, which would eventually shuttle the cargo to the target site. At the breast cancer, Sulphoraphane sensitizes the estrogen receptors and ameliorates the binding affinity of Tamoxifen to these receptors, thereby potentiating the anticancer efficacy and reducing the offsite toxicity of Tamoxifen. This dual loaded zero-dimension lipid carrier would be a value addition to the current treatment regimen for breast cancer management.
乳腺癌是全球第二大致死原因,且不限于女性。他莫昔芬被认为是雌激素受体阳性乳腺癌的黄金一线治疗药物。然而,这种化学预防方法主要针对高风险人群,其临床应用仅限于中危和/或低危人群。此外,他莫昔芬治疗与剂量相关的肝毒性和肾毒性有关,最终导致患者生活质量下降。硫代葡萄糖苷是一种天然的异硫氰酸盐衍生物,因其具有多种潜在的生物学活性而受到研究关注,包括抗癌作用。本研究旨在提出一种新的假说,即将他莫昔芬与天然生物活性硫代葡萄糖苷联合应用,并将其整合到一种新型的脂质纳米载体中,以降低剂量,从而将药物递送到靶位。在乳腺癌中,硫代葡萄糖苷敏化雌激素受体,改善他莫昔芬与这些受体的结合亲和力,从而增强抗癌疗效,降低他莫昔芬的脱靶毒性。这种双载零维脂质载体将为乳腺癌管理的当前治疗方案增加价值。