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

environmentally harmful . In mammals, H S can anticipate that this state-of-the-art review will empower
[1]
2
be endogenously generated through the catalysis of the synthesis of H S-based chemopreventive drugs and
2
L-cysteine and homocysteine by cystathionine γ-lyase promote the need for further in-depth exploration of the
(CSE) and cystathionine β-synthase (CBS), which are the associations between H S and cancer treatments in clinical
2
two members of pyridoxal-5bers of pyri(PLP)-dependent settings.
enzymes that are predominantly found in the cytosol
form . Besides, 3-mercaptopyruvate sulfurtransferase 2. Targeting exogenous H S for cancer
[2]
2
(3-MPST), which is a non-PLP-dependent enzyme, acts treatment
in unison with cysteine aminotransferase (CAT) and 2.1. Natural world
in the presence of α-ketoglutarate to produce H S from
2
L-cysteine. Both enzymes are colocalized in the cytosol 2.1.1. Allicin
and mitochondria . Moreover, it has been indicated that Diallyl thiosulfinate, also known as allicin, is a biologically
[3]
D-amino acid oxidase can catalyze D-cysteine to form active compound found in garlic. Having antitumor
Achiral ketoacid and 3-mercaptopyruvate, which is further and antimicrobial properties, this compound induces
processed by 3-MPST into H S in both the brain and kidneys antitumor activities by regulating cellular processes, such as
2
(Figure 1) . The produced H S is then instantly released apoptosis, inflammation, oxidative stress, autophagy, and
[4]
2
or converted into acid-labile sulfur or bound sulfane angiogenesis . The mechanisms targeted in mediating
[11]
sulfur and stored in mammalian cells . The catabolism its effects include post-translational modifications of the
[5]
of H S can occur through mitochondrial oxidation to protein cell cycle, mitochondria apoptotic pathways, redox-
2
sulfate and thiosulfate, excretion from the kidney or sensitive signaling cascades, catalytic actions of telomerase
lung, sulfhemoglobin-mediated scavenging, and thiol enzyme, and activities of intercellular glutathione (GSH)
methyltransferase and rhodanese-mediated methylation and nucleic acid modifications . The effects of allicin
[12]
to generate methanethiol and dimethylsulfide . vary with different cancers and cell types . It has been
[6]
[13]
Due to its unique chemistry, molecular reactivity shown that the treatment of colon cancer cells (HCT-
mechanisms, ability to modify proteins, and active 116) with allicin can effectively inhibit cell proliferation
participation in many redox reactions with metal, H S by promoting pro-apoptotic events characterized by the
2
has emerged as an essential signaling molecule in cancer upregulation of Bax and cytochrome (Cyt)-c expressions,
biology. A huge volume of research has indicated the key the downregulation of Bcl-2 and Bcl-xL, and subsequently,
roles of H S in a wide range of physiological activities the activation of nuclear factor erythroid-2-related factor 2
2
related to cell cycle and tumorigenesis. H S is involved in (Nrf2) and deactivation of signal transducer and activator of
2
[14]
angiogenesis, tumor growth, cellular and mitochondrial transcription 3 (STAT-3) pathways . The administration
biogenesis, migration and invasion, tumor blood flow, of allicin induces autophagic cell death in liver and thyroid
metastases, epithelial-mesenchymal transition (EMT), cancer through the stimulation of p53 and the inactivation
DNA repair, protein sulfhydration, and chemotherapy of protein kinase B (AKT)/mammalian target of rapamycin
resistance [7-10] . (mTOR) pathway, respectively .
[15]
Since the last decades of research trend in translating In ovarian cancer, glioblastoma, gastric cancer, cervical
H S to therapeutic forms, extensive efforts have been made cancer, and cholangiocarcinoma, the anti-carcinogenic
2
by exploring natural H S-based molecules and designing effects of allicin have been found to be associated with
2
synthetic ones (donors and inhibitors) to exploit the role of the activation of c-Jun N-terminal kinase (JNK) mitogen-
H S in cancer development. H S donors and inhibitors have activated protein kinase (MAPK)/extracellular signal-
2
2
gained importance and are being extensively explored to regulated kinase (ERK) and p38 MAPK/Nrf2 pathways as
[16]
determine their clinical application in research, especially well as the inhibition of STAT-3 cascades . Furthermore,
cancer. The research community is constantly struggling the loss of mitochondria potential, the activation of
to design H S-based pharmacological drugs using these caspases, and the overexpression of p21, NOX4, and Bak
2
molecules and expecting significant breakthroughs in H S have been reported in a breast cancer cellular model
2
[17]
research in cancer. Considering the clinical importance following the treatment with allicin . A recent study
of these naturally existing and those pharmacologically has also revealed that allicin can effectively suppress the
synthesized H S-based chemicals and research trends, it migration and invasion of gastric cancer cells by elevating
2
is worth summarizing the relevant literature that focuses miR-383-5p and inhibiting the receptor protein-tyrosine
on their use in translational research. The present study kinase ERBB4 . In addition, allicin effectively reverses
[18]
provides a detailed discussion of the types of H S donors the oncogenic properties of ornithine decarboxylase in
2
and inhibitors and their role in cancer research. We neuroblastoma .
[19]
Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/gpd.v2i1.164