Page 24 - GPD-2-1

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

of G2/M arrest through the activation of mitochondria cyclin K, and caspases and downregulates the expressions
apoptotic pathway, p21 upregulation, and histone H3 of EGFR, cyclin B1, and Bcl-2 [125] . SFN also suppresses
phosphorylation, accompanied by the activation of ROS- miR-616-5p expression through histone modification,
AMPK pathway [112] . In addition, SFN causes cell death by deactivates the GSK3β/β-catenin pathway to inhibit EMT
inducing cell cycle arrest at the S phase through p21/53 and reduce stem cell-like properties in lung cancer cells,
upregulation and reducing the expressions of suppressor of sensitizes lung cancer cells to treatments by upregulating
variegation, enhancer of zeste, trithorax (SET) and myeloid- miR-214, and inhibits IL-6/ΔNp63α/Notch pathways [126] .
Nervy-DEAF1 domain-containing 3, myosin regulatory In nasopharyngeal carcinoma, SFN suppresses malignancy
light chain 9, as well as cysteine-rich angiogenic inducer [113] . by preventing the reactivation of the Epstein–Barr virus
SFN also promotes the maturation of miR-29a-3p, reduces lytic cycle, increases the expression of Wnt inhibitory
COL3A1 and COL5A1, inhibits the Wnt/β-catenin pathway factor 1, inhibits DNA methyltransferase 1, and inhibits the
phosphorylation of MAPK, deactivates EGFR and p-ERK1/2, activation of STAT-3 through the upregulation of miRNA-
and inhibits the Sonic hedgehog pathway [114] . 124-3p [127] . Besides, in salivary gland adenoid cystic
carcinoma, SFN treatment induces anticancer activities
In prostate cancer, SFN treatment facilitates apoptosis
by increasing mitochondria ROS, apoptotic protease- by mediating G2/M arrest, accompanied by the decrease
in cyclin B1 and CDK1, the increase in caspases and Bax,
activating factor-1, and Bax expression, and reduces the and ultimately the inhibition of NF-κ pathway [128] . Overall,
expression of phosphoglucomutase 3, the activation of the effect of SFN on cancer suppression has been explicitly
caspases, the upregulation of Nrf2, the demethylation of elaborated in different types of cancers, with the critical
cyclin D2, the suppression of androgen receptors, and cellular markers and processes affected being identified.
the inhibition of STAT-3, HDAC6 deacetylase, ERK1/2, With the new focus on the drug clearance mechanism and
hTERT, and C-MYC [115,116] . In a recent study, treatment potential side effects, vital information that might be useful
with N-acetyl-L-cysteine has been reported to inhibit fatty in clinical application can be obtained.
acid metabolism by acetyl-CoA carboxylase and fatty acid
synthase suppression, which, in turn, inhibits prostate cancer 2.1.7. 4-methylthiobutyl isothiocyanate (erucin)
inhibition [117] . SFN also induces the acetylation of histone Another common ITC compound is erucin. The protective
H3 and H4, which leads to cell cycle arrest [118] . SFN has also power of this compound in cells is essentially attributed to
been demonstrated to exert an inhibitory effect on ovarian its H S moiety. In addition to other mechanisms, erucin acts
cancer cell proliferation by attenuating retinoblastoma by regulating apoptosis and inflammatory processes [129] . In
2
protein phosphorylation and E2F-1 expression [119] . Besides, colon cancer, HCC, bladder cancer, prostate cancer, and lung
SFN also triggers G1/G2/M arrest and inhibits the PI3K/ cancer, treatment with erucin suppresses tumor growth and
AKT pathway [120] . In recent studies, SFN has been shown to metastasis by promoting AKT and ERK phosphorylation
increase the sensitivity of ovarian cancer cells to cisplatin by and DNA damage, as well as blocking cell cycle at G2/M
inhibiting NF-κB, HER2, and C-MYC as well as upregulating phase and p21/53 overexpression, respectively [130] . Erucin
p53, p27, Bax, and miR-30a-3p, thus facilitating DNA induces cell death in KRAS-mutated pancreatic cancer
damage [121] . In neuroblastoma, SFN promotes anticancer cell line AsPC-1 by suppressing ERK phosphorylation,
activities through caspase-dependent apoptosis, which is which is a crucial mechanism to counteract KRAS-
mediated by MEK/ERK activation [122] . Furthermore, in associated carcinogenic features associated with MAPK
HCC, SFN reduces the expressions of Bcl-2, HIF-1α, and hyperphosphorylation [131] . Besides, treatment with
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4, erucin can effectively suppress carcinogenic activities by
increases the expression of caspase-3 and Bax, as well as suppressing telomerase activities in ovarian cancer [132] .
activates Nrf2, p38, and ERK pathways to mediate cancer In breast cancer, erucin improves microtubule stability,
cell death [123] . SFN also activates Nrf2/antioxidant response induces cell cycle arrest, mitochondria translocation of
element/heme oxygenase-1, inhibits STAT3/HIF-1α/VEGF, cofilin and dynamin-related protein, mitochondria fission,
and ROS dependently inactivates TGF-β pathway and and the downregulation of HER2 and S6 ribosomal protein
hTERT expression in HCC cells. SFN treatment significantly phosphorylation [133] . Overall, erucin treatment exhibits
increases the demethylation of histone H4 on arginine 3 anticancer activities in different cell types through a variety
(H4R3me2s) in epidermal squamous cell carcinoma through of mechanisms that are altered in cancer.
the alleviation of protein arginine methyltransferase-5 and
methylome protein 50 expressions [124] . 2.1.8. Allyl isothiocyanate (AIC)

In lung cancer, SFN upregulates the expressions of p21, AIC, a natural anti-inflammatory and anticancer
p73, p53 upregulated modulator of apoptosis, Bax, cyclin D1, compound, has been shown to have significant anticancer

Volume 2 Issue 1 (2023) 9 https://doi.org/10.36922/gpd.v2i1.164