As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (H2S) undertakes essential functions, encompassing various signaling complexes that occupy key processes in human biology. Accumulating evidence indicates that H2S exhibits bimodal modulation of cancer development. Thus, endogenous or low levels of exogenous H2S are thought to promote cancer, whereas high doses of exogenous H2S suppress tumor proliferation. Similarly, inhibition of endogenous H2S production also suppresses tumor proliferation. Accordingly, H2S biosynthesis inhibitors and H2S supplementation (H2S donors) are two distinct strategies for the treatment of cancer. Unfortunately, modulation of endogenous H2S on pancreatic cancer has not been studied so far. However, H2S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation, inducing apoptosis, arresting cell cycle, and suppressing invasion and migration through exploiting multiple signaling pathways. As far as we know, there is no review of the effects of H2S donors on pancreatic cancer. Based on these concerns, the therapeutic effects of some H2S donors and NO-H2S dual donors on pancreatic cancer were summarized in this paper. Exogenous H2S donors may be promising compounds for pancreatic cancer treatment.
Keywords: 3-MST, 3-mercaptopyruvate sulfurtransferase; AMPK, adenosine 5′-monophosphate-activated protein kinase; Antitumor effect; BCL-2, B-cell lymphoma-2; BITC, benzyl isothiocyanate; BRCA2, breast cancer 2; CAT, cysteine aminotransferase; CBS, cystathionine-β-synthase; CDC25B, cell division cycle 25B; CDK1, cyclin-dependent kinase 1; CHK2, checkpoint kinase 2; CSE, cystathionine-γ-lyase; Cell proliferation; DATS, diallyl trisulfide; DR4, death receptor; EMT, epithelial–mesenchymal transition; ERK1/2, extracellular signal-regulated kinase; ERU, erucin; FOXM1, forkhead box protein M1; GLUTs, glucose transporters; H2S, hydrogen sulfide; HDAC, histone deacetylase; HEATR1, human HEAT repeat-containing protein 1; HIF-1α, hypoxia inducible factor; Hydrogen sulfide donor; ITCs, isothiocyanates; JNK, c-Jun N-terminal kinase; KEAP1‒NRF2‒ARE, the recombinant protein 1-nuclear factor erythroid-2 related factor 2-antioxidant response element; KRAS, kirsten rat sarcoma viral oncogene; NF-κB, nuclear factor kappa B; NO, nitric oxide; OCT-4, octamer-binding transcription factor 4; P16, multiple tumor suppressor 1; PARP, poly(ADP-ribose)-polymerase; PDGFRα, platelet-derived growth factor receptor; PEITC, phenethyl isothiocyanate; PI3K/AKT, phosphoinositide 3-kinase/v-AKT murine thymoma viral oncogene; Pancreatic cancer; RASAL2, RAS protein activator like 2; ROS, reactive oxygen species; RPL10, human ribosomal protein L10; SFN, sulforaphane; SHH, sonic hedgehog; SMAD4, mothers against decapentaplegic homolog 4; STAT-3, signal transducer and activator of transcription 3; Signaling pathway; Sulfur-containing compound; TRAIL, The human tumor necrosis factor-related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor; XIAP, X-linked inhibitor of apoptosis protein; ZEB1, zinc finger E box-binding protein-1; iNOS, inducible nitric oxide synthase.
© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.