Targeting Pyruvate Kinase M2, β Catenin Signaling by Juglone Silver Nano Framework for Selective Cancer Cell Death,ChemistrySelect

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Targeting Pyruvate Kinase M2, β Catenin Signaling by Juglone Silver Nano Framework for Selective Cancer Cell Death
ChemistrySelect ( IF 1.9 ) Pub Date : 2018-03-13 , DOI: 10.1002/slct.201800152
N. Duraipandy _{1,

2} , Rachita Lakra ₁ , Purna Sai Korrapati _{1,

2} , Perumana R. Sudhakaran ₃ , Manikantan Syamala Kiran _{1,

2}

Affiliation

The modern biomedical nanotechnology necessitates functionalized nanoparticles for targeted action on diseased cells with excellent physico chemical properties. The present study revealed the potential of fabricating juglone silver nano framework for selective cancer cell death by altering the redox states in the cancer cell and selectively inhibiting its growth and proliferation. Conjugation of Juglone with silver nanoparticle reduced the toxicity against normal cells and specifically only inhibited the proliferation of cancer cells. The mechanism of the selective cytotoxic and apoptotic effect on cancer cell was due to down‐regulation of NADPH oxidase 4, Hypoxia‐inducible factor 1α and subdued Pyruvate kinase M2 by arresting Wnt/β catenin signaling through ROS dependent caspase‐3 pathway. Collectively, our findings epitomized that functionalization of nanoparticle gives up a new perspective for adding‐in and tuning the therapeutic values by altering the redox states in cancer cells. Implications of this study opens up a new horizon in modern biomedicine for tuning therapeutic entities to meet the needs of practical applications in complex biological systems.

中文翻译：

Juglone银纳米框架靶向丙酮酸激酶M2，βcatenin信号传导选择性癌细胞死亡

现代生物医学纳米技术需要功能化的纳米粒子，以具有优异的理化性质的靶向作用于患病细胞。本研究揭示了通过改变癌细胞中的氧化还原状态并选择性地抑制其生长和增殖，制造出朱古力银纳米骨架以选择性杀死癌细胞的潜力。Juglone与银纳米颗粒的缀合降低了对正常细胞的毒性，特别是仅抑制了癌细胞的增殖。对癌细胞的选择性细胞毒性和凋亡作用的机制是由于NADPH氧化酶4，低氧诱导因子1α的下调和通过经由ROS依赖性caspase-3途径阻止Wnt /βcatenin信号传导减弱了丙酮酸激酶M2所致。总的来说，我们的发现表明，纳米粒子的功能化为通过改变癌细胞中的氧化还原状态来增加和调节治疗价值提供了新的视角。这项研究的意义为调节治疗实体以满足复杂生物系统的实际应用需求开辟了现代生物医学的新视野。

更新日期：2018-03-13

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