Balakrishnan Solaimuthu, Mukherjee Sudip, Das Sourav, Bhat Firdous Ahmad, Raja Singh Paulraj, Patra Chitta Ranjan, Arunakaran Jagadeesan
Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana State, India.
Cell Biochem Funct. 2017 Jun;35(4):217-231. doi: 10.1002/cbf.3266. Epub 2017 May 12.
Epidermal growth factor plays a major role in breast cancer cell proliferation, survival, and metastasis. Quercetin, a bioactive flavonoid, is shown to exhibit anticarcinogenic effects against various cancers including breast cancer. Hence, the present study was designed to evaluate the effects of gold nanoparticles-conjugated quercetin (AuNPs-Qu-5) in MCF-7 and MDA-MB-231 breast cancer cell lines. Borohydride reduced AuNPs were synthesized and conjugated with quercetin to yield AuNPs-Qu-5. Both were thoroughly characterized by several physicochemical techniques, and their cytotoxic effects were assessed by MTT assay. Apoptotic studies such as DAPI, AO/EtBr dual staining, and annexin V-FITC staining were performed. AuNPs and AuNPs-Qu-5 were spherical with crystalline nature, and the size of particles range from 3.0 to 4.5 nm. AuNPs-Qu-5 exhibited lower IC value compared to free Qu. There was a considerable increase in apoptotic population with increased nuclear condensation seen upon treatment with AuNPs-Qu-5. To delineate the molecular mechanism behind its apoptotic role, we analysed the proteins involved in apoptosis and epidermal growth factor receptor (EGFR)-mediated PI3K/Akt/GSK-3β signalling by immunoblotting and immunocytochemistry. The pro-apoptotic proteins (Bax, Caspase-3) were found to be up regulated and anti-apoptotic protein (Bcl-2) was down regulated on treatment with AuNPs-Qu-5. Additionally, AuNPs-Qu-5 treatment inhibited the EGFR and its downstream signalling molecules PI3K/Akt/mTOR/GSK-3β. In conclusion, administration of AuNPs-Qu-5 in breast cancer cell lines curtails cell proliferation through induction of apoptosis and also suppresses EGFR signalling. AuNPs-Qu-5 is more potent than free quercetin in causing cancer cell death, and hence, this could be a potential drug delivery system in breast cancer therapy.
表皮生长因子在乳腺癌细胞的增殖、存活和转移中起主要作用。槲皮素是一种生物活性黄酮类化合物，已显示出对包括乳腺癌在内的多种癌症具有抗癌作用。因此，本研究旨在评估金纳米颗粒偶联槲皮素（AuNPs-Qu-5）对MCF-7和MDA-MB-231乳腺癌细胞系的影响。通过硼氢化钠还原法合成金纳米颗粒，并将其与槲皮素偶联，得到AuNPs-Qu-5。二者均通过多种物理化学技术进行了全面表征，并通过MTT法评估了它们的细胞毒性作用。进行了诸如DAPI、AO/EtBr双重染色和膜联蛋白V-FITC染色等凋亡研究。金纳米颗粒和AuNPs-Qu-5呈球形且具有晶体性质，颗粒大小范围为3.0至4.5纳米。与游离槲皮素相比，AuNPs-Qu-5表现出更低的IC值。在用AuNPs-Qu-5处理后，凋亡细胞数量显著增加，同时可见核浓缩增加。为了阐明其凋亡作用背后的分子机制，我们通过免疫印迹和免疫细胞化学分析了参与凋亡和表皮生长因子受体（EGFR）介导的PI3K/Akt/GSK-3β信号传导的蛋白质。在用AuNPs-Qu-5处理后，促凋亡蛋白（Bax、半胱天冬酶-3）上调，抗凋亡蛋白（Bcl-2）下调。此外，AuNPs-Qu-5处理抑制了EGFR及其下游信号分子PI3K/Akt/mTOR/GSK-3β。总之，在乳腺癌细胞系中给予AuNPs-Qu-5可通过诱导凋亡来减少细胞增殖，同时还抑制EGFR信号传导。AuNPs-Qu-5在导致癌细胞死亡方面比游离槲皮素更有效，因此，这可能是乳腺癌治疗中的一种潜在药物递送系统。
