Characterization and apoptotic effect of copper nanoparticles biosynthesized from Ziziphus zizyphus leaf on human renal
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ORIGINAL ARTICLE
Characterization and apoptotic effect of copper nanoparticles biosynthesized from Ziziphus zizyphus leaf on human renal cell carcinoma A498 cells Xianduo Li1,2,3 · Guanbao Tang2,3 · Xuewen Guo2,3 · Tongyi Men2,3 Received: 18 July 2020 / Accepted: 25 September 2020 © King Abdulaziz City for Science and Technology 2020
Abstract Biological formulation of copper nanoparticles (Cu-Nps) in cancer treatment has augmented due to its beneficial and curative effects. Ziziphus zizyphus (ZZ) is a species of medicinal plant traditionally used for various ailments. Hence, this work deals with formulation of copper nanoparticles (Cu-NP’s) from Z. zizyphus leaf extracts (Cu-ZZ NP’s) and examine its effect on human renal carcinoma A498 cells. The characterization of the formulated Cu-ZZ NPs was done by spectroscopic and microscopic methods. The anti-cancer tests (MTT, ROS, MMP, Hoechst staining, comet, Real‐time PCR, and western blot) were used to evaluate the biological properties of Cu-ZZ NPs on the growth and proliferation of A498 cells. The cytotoxic activity of Cu-ZZ NPs resulted in potent toxicity of A498 cells. Further, Cu-ZZ NP’s triggered an intracellular ROS generation through mitochondrial pathways in the A498 cells, revealing a noteworthy cytotoxicity activity. Also, fluorescent microscopic studies using Hoechst staining, and comet analysis confirmed the occurrence of apoptosis in Cu-ZZ NPs treated A498 cells. Following, quantitative RT-PCR presented a negative regulation of Bcl-2 expression and positive regulation of Bid, Bax, and caspases (3 and 9) gene expression in Cu-ZZ NP’s treated A498 cells. To further justify, inhibition of mTOR/ PI3K/AKT protein expression by Cu-ZZ NPs in A498 cells, lead to an inference that Cu-ZZ NPs induce apoptosis in A498 cells by inhibiting the mTOR, PI3K/Akt pathway. Keywords Renal cell carcinoma · Metastasis · Copper nanoparticles · Ziziphus zizyphus
Introduction Cancer is one of the most debilitating health issues with annual cases reported to be reaching 22 million in 2019 by the World Health Organization (WHO). Recently, for reasons that are not known, the number of new kidney cancers has been mounting since the 2000s (Znaor et al. 2015). Kidney cancer is the ninth common cancer among males and 14th among females. Veritably, almost 80% of kidney cancers * Tongyi Men [email protected] 1
School of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan City 250012, Shandong Province, China
2
Department of Urology, The First Affiliated Hospital of Shandong First Medical University, No. 16766 Jingshi Road, Jinan City 250014, Shandong Province, China
3
Department of Urology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan City 250014, Shandong Province, China
are carcinomas or commonly known as renal cell carcinoma (RCC) (Lin et al. 2014). Histologically, RCC affects the lining of the kidney tubules, characterized by pale and abundant eosinophilic cytoplasm, large and prominent nuclei with and nuclear
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