钌
化学
癌症研究
连环素
PI3K/AKT/mTOR通路
细胞凋亡
连环蛋白
调制(音乐)
信号
肺癌
内科学
细胞生物学
医学
Wnt信号通路
生物
物理
生物化学
信号转导
声学
催化作用
作者
Sakuntala Gayen,Souvik Roy,Diana Laishram,Subir Bandyopadhyay,Swarupananda Mukherjee
标识
DOI:10.1111/1440-1681.70030
摘要
ABSTRACT Lung cancer is most terrible cause of cancer‐related death throughout the world. This study focused on the synthesis and characterisation of novel flavokawain A ruthenium‐p‐cymene complex and to investigate the chemotherapeutic activity against lung carcinoma via in silico, in vitro and in vivo approaches. The complex was characterised via several spectroscopic techniques. In vitro study including cell viability, transwell migration, Western blot and flow cytometric analysis have been executed on both A549 and NCI‐H460 cells. The toxicological assessment was performed and subsequently anticancer activity of complex was evaluated in benzo[α]pyrene persuaded lung carcinoma in mice. The molecular docking study demonstrated the compound has greater binding ability with β‐catenin, Akt, HER2 and PARP. Followed by the complex treatment, the downregulation of β‐catenin, PI3K, Akt, HER2 and PARP were investigated by Western blot analysis and cell cycle arrest was determined through flow cytometry. The outcomes of in vivo experimentation represented fruitful restoration of typical lung architecture after complex treatment. Immunohistochemical analysis demonstrated the downstream of β‐catenin/m‐TOR/Akt and upstream of caspase‐3 and p53 expression, thereby initiating apoptosis. The complex exhibited a potent chemotherapeutic activity via the alteration of tumour microenvironment by modulating PI3K/Akt/β‐catenin/HER2/PARP transduction in correlates with apoptotic events in lung carcinoma.
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