Study of the Mechanism by Which Curcumin Cooperates with Sestrin2 to Inhibit the Growth of Pancreatic Cancer

Abstract

Background. Pancreatic carcinoma is a malignant tumor with a high fatality rate, and the increased resistance of pancreatic carcinoma to chemotherapy has become a difficult problem in clinical practice. Hence, it is imperative to develop an effective treatment for pancreatic cancer. Sestrins are a class of stress-induced proteins that have antioxidation functions, regulating cell growth and metabolism. Curcumin is a natural pigment isolated from turmeric. Several studies have also suggested that this molecule has multiple pharmacological effects, such as anti-inflammatory, antioxidant, and antitumor effects. However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. Our aim was to observe the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms. Methods. Lentiviral infection, real-time fluorescence quantitative PCR assays, Cell Counting Kit-8 assays, real-time cell analysis technology, colony formation assays, wound healing assays, Transwell invasion assays, protein extraction, and western blots (WBs) were used to evaluate the effect of curcumin combined with sestrin2 on the proliferation, invasion, and migration of pancreatic carcinoma cells. Results. The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer. In addition, we determined that sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1. Conclusion. These findings clarify that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer.

Discovery of BAR502, as potent steroidal antagonist of leukemia inhibitory factor receptor for the treatment of pancreatic adenocarcinoma

“…In addition to KIF20A, BAR502 potently downregulated the expression of the Ribonucleotide reductase subunit M2 (RRM2), (FC: -14,34) ( 68 ) and TNF Receptor Superfamily Member 1B (TNFRSF1B or TNFR2) (FC: -11,72) ( 69 ) and DNA topoisomerase II alpha (TOP2A) (FC: -9,61), an important regulator of DNA replication and cell cycle progression and up-regulated in PDAC ( 70 ). On the other hand, exposure to BAR502 increased the expression of a number of genes, including the Solute carrier family 7 member 11 (SLC7A11) (FC: 35,54), a cysteine transporter involved in the inhibition of the ferroptosis programmed cell death ( 71 ), that was the most upregulated gene, and the Cyclin D2 (CCND2) (FC: 16,13) ( 72 ) and Sestrin 2 (SESN2) (FC: 15,84) ( 73 ),, whose expression are robustly reduced in PDAC cells ( 74 ).…”

Impacts of turmeric and its principal bioactive curcumin on human health: Pharmaceutical, medicinal, and food applications: A comprehensive review

“…However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. A study carried out (193) observed the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms. The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer.…”

“…In addition, sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1. It is concluded that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer (193). In another study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield.…”

Sestrin2 in cancer: a foe or a friend?

“…Meanwhile, Sestrin2 expression decreases in higher stages of the tumor and positively correlates with patients’ survival [ 116 ]. Furthermore, lentiviral-mediated upregulation of Sestrin2 has been associated with inhibition of pancreatic cancer cells proliferation, invasion, and migration in PANC-1 and CFPAC-1 cell lines [ 117 ].…”