Trace elements in pancreatic cancer

Abstract

Background: Pancreatic cancer (PCA) is an extremely aggressive malignant cancer with an increasing incidence and a low five-year survival rate. The main reason for this high mortality is that most patients are diagnosed with PCA at an advanced stage, missing early treatment options and opportunities. As important nutrients of the human body, trace elements play an important role in maintaining normal physiological functions. Moreover, trace elements are closely related to many diseases, including PCA.

Review: This review systematically summarizes the latest research progress on selenium, copper, arsenic, and manganese in PCA, elucidates their application in PCA, and provides a new reference for the prevention, diagnosis and treatment of PCA.

Conclusion: Trace elements such as selenium, copper, arsenic and manganese are playing an important role in the risk, pathogenesis, diagnosis and treatment of PCA. Meanwhile, they have a certain inhibitory effect on PCA, the mechanism mainly includes: promoting ferroptosis, inducing apoptosis, inhibiting metastasis, and inhibiting excessive proliferation.

Keywords: arsenic; copper; manganese; pancreatic cancer; selenium; trace elements.

FIGURE 1

Association between trace element levels and pancreatic cancer incidence.

FIGURE 2

Mechanism of selenium in anti‐pancreatic cancer. Selenium is involved in APCA through inducing apoptosis, promoting ferroptosis, inhibiting metastasis, and inhibiting excessive proliferation. ATF3, activating transcription Factor 3; Bax, Bcl2‐associated x; Caspase, cysteinyl aspartate specific proteinase; CD29, β1‐integrin; CDC24, cell division control protein 42 homolog; CEMIP, cell migration inducing hyaluronic binding protein; DDR2, discoidin domain receptor 2; NF‐κB, nuclear factor κB; P4HA1, prolyl 4‐hydroxylase alpha polypeptide 1; PLOD2, procollagen‐lysine,2‐oxoglutarate 5‐dioxygenase 2; ROS, reactive oxygen species.

FIGURE 3

Mechanism of copper in anti‐pancreatic cancer. Copper is involved in APCA through promoting apoptosis, promoting ferroptosis, inhibiting metastasis, promoting autophagy, and targeting tumor DNA damage.AKT/STAT3, serine/threonine kinase/signal transducer and activator of transcription 3 signaling pathway; AMPK/mTOR, adenosine monophosphate‐activated protein kinase/mammalian target of rapamycin signaling pathway. ATF6, activating transcription Factor 6; Bip, heavy chain‐binding protein; CHOP, c/ebp homologous protein; DDIT3, DNA damage inducible transcript 3; GPX4, glutathione peroxidase 4; MAPK, mitogen‐activated protein kinase signaling pathway; ROS, reactive oxygen species; Sp1, specificity protein 1.

FIGURE 4

Mechanism of arsenic in anti‐pancreatic cancer. Arsenic is involved in APCA through promoting apoptosis, inhibiting metastasis, and inhibiting excessive proliferation. Caspase, cysteinyl aspartate specific proteinase; CD24, innate immunosuppressive factor; CD44, cell surface adhesion molecule; EGFR, epidermal growth factor receptor; MMP2, matrix metalloproteinase 2; NF‐κB, nuclear factor κB. Pirh2, p53‐dependent ubiquitin ligase; Skp2, S‐phase kinase‐associated protein 2; TIMP1/PI3K/AKT/mTOR, tissue inhibitor of matrix metalloproteinases 1/phosphoinositide 3‐kinase/serine/threonine kinase/mammalian target of rapamycin signaling pathway; VEGF‐C, vascular endothelial growth factor‐C.

FIGURE 5

Mechanism of manganese in anti‐pancreatic cancer. Manganese is involved in APCA through mainly promoting ferroptosis and inhibiting excessive proliferation. JAK2/STAT3, Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway; MAPK, mitogen‐activated protein kinase signaling pathway; ROS, reactive oxygen species.

FIGURE 6

Mechanism of other trace elements in anti‐pancreatic cancer. This figure describes the APCA mechanisms associated with other trace elements, including inducing apoptosis, promoting ferroptosis, inhibiting metastasis, and inhibiting excessive proliferation. HIF‐1α, hypoxia‐inducible factor‐1α; MUC4, transmembrane glycoprotein; DCBP, syndecan binding protein.