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Gene & Protein in Disease Therapeutic opportunities in hydrogen sulfide for cancer research

organelle. According to preliminary studies, H S induces a naproxen derivative [2-(6-methoxynapthalen-2-yl)-
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cytoprotective effects by promoting oxidative stress, propionic acid 4-thiocarbamoyl phenyl ester]. In addition
apoptosis, and inflammation [217] . Treatment with AP39 has to producing H S, it inhibits COX-2 activity. The previous
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been shown to increase the population of early and late studies have shown that treatment with ATB-346 can
apoptotic cells among colon cancer cells [218] . In addition, significantly reduce colonic pre-cancerous lesions in mice,
it also protects against doxorubicin-induced cardiotoxicity, prostaglandin, and whole-blood thromboxane synthesis
which is associated with mitochondrial toxicity and without causing gastrointestinal injury [226] . The anticancer
a decrease in H S level [219] . Despite the lack of vital effects of ATB-346 are associated with the inhibition of
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information on the mechanisms and pathways targeted by C-MYC and β-catenin expressions. Similarly, treating
this donor in different types of cancers, the available data melanoma cells with ATB-346 inhibit pro-survival
suggest a potential anticancer effect and protective effect activities by suppressing NF-κB and AKT pathways [227] .
when combined with other drugs. This suggests that the donor ATB-346 has anticancer
activities and can be used to treat different types of cancers.
2.3.5. Ammonium tetrathiomolybdate (ATTM)
ATTM is a slow-releasing inorganic H S donor with 2.4. Hydrogen sulfide-nitric oxide (H S-NO) donors
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cytoprotective capability. The chemical formula of 2.4.1. NOSH-aspirin (NBS-1120)
ATTM is (NH ) MoS . ATTM has been shown to exert
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antioxidant effects at lower concentrations in HaCaT Both NO and H S are powerful neuromodulators, and
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cells [220] . Treating pancreatic cancer cell lines with ATTM their role in cancer is widely recognized. The two gaseous
dose and time dependently reduces intracellular high neuromodulators regulate one another. For the donor to
affinity copper uptake protein 1, VEGF, and cyclin D1 logically contain the moiety for both gasotransmitters, it
expressions, thus mediating anticancer activities [221] . induces a more substantial regulatory effect. According
In head-and-neck squamous cell carcinoma, ATTM to a previous study, NBS-1120 exhibits chemoprotective
has been reported to suppress resistance to cisplatin by properties in the gastrointestinal tract, which are
attenuating the progression of cancer by downregulating inextricably linked to its antioxidant and anti-inflammatory
the expression of ATPase copper transporting beta effects, thus making it superior to aspirin [228] . Moreover,
(ATP7B) [222] . Similarly, in breast cancer, treatment with treating colon cancer cells with NOSH-aspirin significantly
ATTM reduces the expression of ATP7A, a copper ATPase facilitate apoptosis, G0/G1 arrest, ROS generation, and
transporter that is involved in the intercellular movement NF-κB deactivation [229] . Mechanistically, NOSH-aspirin
and sequestering of cisplatin, thereby potentiating mediates both S-sulfhydration and S-nitrosylation of p65
cisplatin’s nuclear bioavailability, which, in turn, promotes NF-κB, along with the denitrosylation and desulfhydration
DNA damage, cell cycle arrest, and apoptosis [223] . The of caspase-3, thereby inhibiting the activation of caspase-3
safety, tolerance, and anticancer effects of recurrent breast and NF-κB [230] . According to another study, the compound
cancer in patients have been witnessed in a clinical study preferentially inhibits COX-1 over COX-2, and its effect
involving the drug [224] . Moreover, treating lung cancer varies with different isomers, with the inhibitory effect
cells with ATTM significantly increase the expression in colon cancer ranking as follows: o-NOSH-aspirin
of H S-producing enzymes CBS and 3-MPST and > m-NOSH-sspirin > p-NOSH-aspirin [231] . In a mice
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promote cancer progression at low concentrations, with colon cancer model, the combination of NOSH-aspirin
an opposite effect at higher concentrations [225] . At lower with 5-fluorouracil induced a stronger effect compared to
concentrations, ATTM triggers YTHDF1-dependent individual treatments and showed no side effects or weight
PRPF6 m A methylation through the upregulation of loss in mice [232,233] . In breast cancer, the drug treatment
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methyltransferase-like protein 3 and the downregulation results in tumor suppression through the reduction of
of fat mass and obesity associated-protein (FTO). Overall, proliferating cell nuclear antigen, an increase in cyt c,
these data suggest that ATTM shows potential in cancer and ROS generation [234] . Similarly, a recent study has
treatment; however, the information available on the revealed that the treatment with NOSH-aspirin exerts
mechanism of action involved is insufficient. anticancer effects in a mice model of pancreatic cancer
by increasing ROS generation, caspase-3 activity, and
2.3.6. H S-releasing nonsteroidal anti-inflammatory mutated p53 expression, while suppressing NF-κB and
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drugs (H S-NSAIDs) [235]
2 FoxM1 expressions . Overall, the above data suggest that
H S-NSAIDs are H S-moiety-containing anti- NOSH-aspirin can be used to treat cancer, with minimal
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inflammatory drugs with potent anticancer properties. side effects and by primarily targeting the cell cycle, COX-
One of the most common H S-NSAIDs is ATB-346, 1/2, and ROS.
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Volume 2 Issue 1 (2023) 14 https://doi.org/10.36922/gpd.v2i1.164