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Sains Malaysiana 51(12)(2022):
http://doi.org/10.17576/jsm-2022-5112-11
The Anti-Tumor Effect of
Zinc on Renal Cell Carcinoma by Enhancing Autophagy
(Kesan Anti-Tumor Zink ke atas Karsinoma Sel Renal dengan Mempertingkatkan Autofagi)
ZHIHAI YU1, SHAOBO WU2, QIURONG ZHAO2,
YAOCHUAN GUO1, HENGCHUAN LIU1 & XIAO HUANG3,*
1Department of Urology, Chongqing University
Three Gorges Hospital, Chongqing 404000, China
2Central Laboratory, Chongqing University
Three Gorges Hospital, Chongqing 404000, China
3School of Physical Education, Guangxi
University of Science and Technology, Liuzhou 545006, China
Received:
28 July 2021/Accepted: 15 August 2022
Abstract
Renal cell carcinoma remains one of the most common malignant tumorsand is associated with significant challenges in drug therapy. Zinc has been reported to be of
pharmacological importance and immense
potential in the inhibition of renal cell carcinoma cells. In
order to investigate the inhibitory effect of zinc on the human renal cell carcinoma cell line A498, its anti-proliferative activity was investigated using the CCK8 assay. The oxidative stress status and mitochondrial injury were
detected by DCFH-DA and JC-1 staining, respectively. The expression of
autophagy-related proteins was determined by western blot analysis, which aimed at exploring the antioxidant mechanisms of zinc. Over 40% yield of ROS and more than four times the number of autophagosomes were detected in the experimental group
treated by zinc compared to the control group. Furthermore, zinc led to up-regulation of the Beclin 1-related signaling pathway in the late stage of
autophagy degradation. Zinc demonstrated a
good inhibitory effect on A498 cells with the value of IC50similar to the values of natural products. One of the mechanisms of zinc is enhancing the Beclin 1-dependent autophagy. Taken together, with its low
cost and natural properties, zinc could become a promising molecule with satisfied anti-tumor effect and low
cost in the treatment of renal cell
carcinoma.
Keywords: Autophagy; mitochondrial membrane potential; oxidative stress; renal cell carcinoma; zinc
Abstrak
Karsinoma
sel renal kekal sebagai salah satu tumor malignan yang paling biasa dan dikaitkan
dengan cabaran penting dalam terapi dadah. Zink telah
dilaporkan mempunyai kepentingan farmakologi dan potensi besar dalam perencatan
sel karsinoma sel renal. Untuk
mengkaji kesan perencatan zink pada sel karsinoma sel renal manusia A498,
aktiviti anti-proliferatifnya telah dikaji menggunakan asai CCK8. Status
tekanan oksidatif dan kecederaan mitokondria dikesan oleh pewarnaan DCFH-DA dan
JC-1. Ekspresi protein berkaitan
autofagi ditentukan oleh analisis pemblotan western yang bertujuan untuk meneroka
mekanisme antioksidan zink. Lebih 40%
hasil ROS dan lebih daripada empat kali bilangan autofagosom dikesan dalam
kumpulan uji kaji yang dirawat dengan zink berbanding dengan kumpulan kawalan. Tambahan
pula, zink membawa kepada pengawalseliaan tapak jalan pengisyaratan
berkaitan-Beclin 1 pada peringkat akhir pendegradan autofagi. Zink
menunjukkan kesan perencatan yang baik pada sel A498 dengan nilai IC50 sama seperti nilai produk semula jadi. Salah satu
mekanisme zink ialah meningkatkan autofagi bersandar-Beclin 1. Jika
digabungkan, dengan kos rendah dan sifat semula jadi, zink boleh menjadi
molekul berpotensi dengan kesan anti-tumor yang memuaskan dan kos rendah dalam
rawatan karsinoma sel renal.
Kata kunci: Autofagi; karsinoma sel renal; potensi membran mitokondria; stres oksidatif; zink
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*Corresponding author; email: humphrey8531@hotmail.com
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