New possible silver lining for pancreatic cancer therapy: Hydrogen sulfide and its donors

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.