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

radiosensitivity of cancer cells by suppressing the nuclear reactive oxygen species (ROS)-induced apoptosis and the
factor-kappa B (NF-κB) signaling pathway in CRC and activation of JNK/p38 cascade .
[27]
[25]
through the promotion of intracellular DNA damage that In a human study of basal cell carcinoma, the patients
is related to the downregulation of interleukin (IL)-6 and were topically treated with ajoene. The study showed that
interferon-β as well as the increase in p53 expressions in ajoene can effectively suppress tumor growth through the
glioblastoma . Despite the promising anticancer effects activation of mitochondria-dependent apoptosis and the
[28]
of allicin, a recent study has shown that allicin can trigger subsequent reduction of antiapoptotic Bcl-2 expression .
[35]
hemolysis, eryptosis, and oxidative stress in erythrocytes Besides, apoptotic regulators such as p53, p63, and p73 have
through calcium overload and the activation of MAPK and also been demonstrated to be activated by the compound in
[29]
casein kinase-1α . The combined treatment of allicin with cellular models . Furthermore, Z-ajoene could selectively
[36]
eryptosis inhibitors could be helpful in reducing the effect. inhibit cancer stem cells from glioblastoma multiform by
In recent years, nanoparticles have been established as attenuating phosphorylated (p)-SMAD4, p-AKT, and
effective and efficient carriers for delivering numerous drugs. FOXO3A expressions . In MDA-MB-231 and HeLa
[37]
In the case of allicin, its cytotoxicity in HepG2 cells has cancer cells, ajoene has shown to reduce migration and
been demonstrated to be enhanced with the encapsulation invasion activities through s-thiolation of cysteine-328
of gelatin nanoparticles coated with glycyrrhetinic acid . of the vimentin, thereby disrupting it and subsequently
[30]
Moreover, the loading of allicin with cyclodextrin-based inhibiting metastatic activities .
[38]
nanoparticles also enhances its delivery and the resulting An analog of ajoene, bis[(para-methoxy) benzyl], has
corresponding pro-apoptotic effect on cancer cells . Overall, more substantial anticancer effects. It acts by activating
[31]
allicin has shown promising anticancer activity. In addition, unfolded protein response mechanisms through CHOP/
it is cost-efficient and can be used in combination with other growth arrest- and DNA damage-inducible protein 153
drugs to increase sensitivity and alleviate side effects.
(GADD153) in esophageal carcinoma . In the treatment
[39]
2.1.2. Ajoene of colon cancer cells, Z-ajoene effectively inhibits tumor
growth by decreasing the expression of β-catenin and
The anticancer properties of ajoene have been widely increasing CK-1α-mediated β-catenin phosphorylation
recognized and attentively investigated. Ajoene and prevents skeletal muscle atrophy induced by colon
(4,5,9-trithiadodeca-1,6,11-triene-9-oxide) is a sulfur- cancer by suppressing muscle-specific E3 ligases and
containing organic compound formed after the NF-κB . Therefore, ajoene can specifically and selectively
[40]
rearrangement of allicin. Ajoene occurs in two forms: target cancer cells as well as promote apoptosis and
Z- and E-isomers. By characterization, the former is antimetastatic activities.
more bioactive, while the latter is relatively more stable.
Recently, the compound has been shown to be synthesized 2.1.3. Diallyl sulfide (DAS)
in the laboratory through a new technique involving
four key steps: (1) propargylation; (2) radical addition of DAS is a significant component of garlic with protective
thioacetate; (3) deprotection; and (4) disulfide formation/ properties against various physiological disorders. The
allylation. Ajoene has antimicrobial, antithrombosis, regulation of cellular markers associated with apoptosis,
redox status, necrosis, angiogenesis, and cytotoxicity
anti-inflammatory, and anticancer properties . In (cytochrome P450 2E1), as well as the interaction with
[32]
cancer, the compound targets several activities, such membrane lipids are among the mechanisms targeted
as migration, apoptosis, oxidative stress, and protein by the compound . In cancer, DAS has been previously
[41]
folding . A previous study has suggested that ajoene shown to delay the onset of cancer in chemically induced
[33]
can induce anticancer effects in leukemia cells (HL-60) [42]
by triggering G2/M arrest, attenuating proteasome- skin tumors in mice . The corresponding effects of DAS
mediated trypsin- and chymotrypsin-like activities as are associated with the inhibition of key cellular pathways,
well as inhibiting ERK-1/2 signaling cascade . Moreover, such as p53, p21/Ras, PI3K/AKT, and p38 MAPK cascades,
[34]
[43]
the ajoene has been shown to promote apoptosis in with JNK1 and ERK1/2 remaining unaffected . In vitro
leukemic cells but not in peripheral mononuclear blood evidence has revealed that DAS can effectively protect
cells of healthy individuals by elevating the oxidative normal human breast cells MCF-10A from a carcinogenic
[25]
status and activating the NF-κB pathway . Similarly, chemical compound, diethylstilbestrol, which can cause
[44]
in lung adenocarcinoma, the treatment with 25 µM of DNA damage and lipid peroxidation .
ajoene significantly reduced the cell viability of cancerous In prostate cancer, DAS has been shown to improve
cells A549, NCI-H1373, and NCI-H1395, but not non- oxidative status by suppressing a testosterone-mediated
carcinogenic bronchus cells BEAS-2B, partially through decrease in antioxidants . It has also been reported that
[45]

Volume 2 Issue 1 (2023) 4 https://doi.org/10.36922/gpd.v2i1.164