Sains Malaysiana 51(12)(2022): 4009-4018

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 HUANG^3,*

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

Diserahkan: 28 Julai 2021/Diterima: 15 Ogos 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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