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Review
. 2024 Feb 2:15:1333543.
doi: 10.3389/fphar.2024.1333543. eCollection 2024.

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer

Pengtuo Xiao  1 , Changfeng Li  1 , Yuanda Liu  1 , Yan Gao  2 , Xiaojing Liang  2 , Chang Liu  1 , Wei Yang  2
Affiliations
Review

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer

Pengtuo Xiao et al. Front Pharmacol. .

Abstract

Metal ions exert pivotal functions within the human body, encompassing essential roles in upholding cell structure, gene expression regulation, and catalytic enzyme activity. Additionally, they significantly influence various pathways implicated in divergent mechanisms of cell death. Among the prevailing malignant tumors of the digestive tract worldwide, gastric cancer stands prominent, exhibiting persistent high mortality rates. A compelling body of evidence reveals conspicuous ion irregularities in tumor tissues, encompassing gastric cancer. Notably, metal ions have been observed to elicit distinct contributions to the progression, drug resistance, and biological attributes of gastric cancer. This review consolidates pertinent literature on the involvement of metal ions in the etiology and advancement of gastric cancer. Particular attention is directed towards metal ions, namely, Na, K, Mg, Ca, Fe, Cu, Zn, and Mn, elucidating their roles in the initiation and progression of gastric cancer, cellular demise processes, drug resistance phenomena, and therapeutic approaches.

Keywords: calcicoptosis; cuproptosis; drug resistance; ferroptosis; gastric cancer; metal ion.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The role of metal ions in the development, cell death and treatment of gastric cancer.
FIGURE 2
FIGURE 2
Diagram of sodium ion channels in normal gastric tissue and NOCs induced by high sodium promoting gastric cancer.
FIGURE 3
FIGURE 3
Diagram of the relationship between lipid peroxidation and ferroptosis. The process of lipid peroxidation in cells is mainly catalyzed by the lipid peroxidation process catalyzed by fatty acid enzymes and the Fenton reaction induced by free iron ions. At the same time, the clearance of lipid peroxidation in cells mainly relies on the action of glutathione peroxidase 4 (GPX4).
FIGURE 4
FIGURE 4
(A) Cu chelating agents reduce Cu bioavailability; (B) Cu ionophores deliver Cu into cells to increase intracellular Cu levels. Excessive Cu induces oligomerization of Lipoyl Acyltransferase (DLAT). The oligomerization of DLAT leads to cell toxicity and induces cell death. At the same time, FDX1 reduces Cu2+ to more toxic Cu+, ultimately leading to inactivation of Fe-S proteins. Together, they induce protein toxicity stress, ultimately resulting in cell death.
FIGURE 5
FIGURE 5
(A) ZnO-NP can reduce tumor growth of chemotherapy-resistant GC cells in vivo. Adopted from MIAO Y H, MAO L P, CAI X J, et al. Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy. World J Gastroenterol, 2021, 27 (25): 3,851-62; (B) TP-ZnO-NP has significant anti-proliferation and anticancer activity on gastric cancer cells. TP-ZnO-NPs demonstrated better inhibition on the proliferation and colony formation of gastric cancer cells compared with cisplatin. Adopted from BOZGEYIK I, EGE M, TEMIZ E, et al. Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition. Gene, 2023, 853: 147091.
FIGURE 6
FIGURE 6
Diagram of calcium overload leading to cell death.
FIGURE 7
FIGURE 7
Schematic diagram of potential pathways for metal ion treatment of gastric cancer.
See this image and copyright information in PMC

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