The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

Abstract

Nitric oxide (NO) a gaseous free radical is one of the ten smallest molecules found in nature, while hydrogen sulfide (HS) is a gas that bears the pungent smell of rotten eggs. Both are toxic yet they are gasotransmitters of physiological relevance. There appears to be an uncanny resemblance between the general actions of these two gasotransmitters in health and disease. The role of NO and HS in cancer has been quite perplexing, as both tumor promotion and inflammatory activities as well as anti-tumor and antiinflammatory properties have been described. These paradoxes have been explained for both gasotransmitters in terms of each having a dual or biphasic effect that is dependent on the local flux of each gas. In this review/commentary, I have discussed the major roles of NO and HS in carcinogenesis, evaluating their dual nature, focusing on the enzymes that contribute to this paradox and evaluate the pros and cons of inhibiting or inducing each of these enzymes.

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

“…However, in hypertensive conditions, NaHS treatment attenuated maternal hypertension and improved feto‐placental parameters. Researchers state that H 2 S may exert dual effects, and although these effects are not fully comprehended, especially in the cardiovascular system, our results regarding normotensive vs hypertensive pregnant rats treated with NaHS support this concept.…”

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients

“…Several studies have ascertained that NO and H 2 S have a dichotomous role in cancer, either promoting growth and proliferation. In contrast, others suggest antitumor effects such as inhibition of cell proliferation and suppression of DNA synthesis of the cancer cells as remarked by Kashefi in a recent review 32 . Given the positive role of these two gasotransmitters in the inhibition of cancer cell proliferation, in the present study, we have investigated the effect of NO and H 2 S donors individually or in combination with 5-FU on the HT-29 cell line for 24hrs.…”

S-nitrosothiols and H2S donors: Potential chemo-therapeutic agents in cancer

“…This has been observed for the anti-inflammatory-H 2 S hybrids used in the treatment of osteoarthritis [99]. Various H 2 S [26,102] and NO-releasing compounds [24] have been developed that are of relevance to cancer chemotherapy.…”