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

DAS can potentially induce antiproliferative properties in arrest by activating cyclin B1 and promoting apoptosis
thyroid carcinoma by activating the mitochondria apoptotic through ROS-mediated activation of p53 pathway, thereby
pathway as displayed by the elevation of Bax, caspase-3, -9, promoting cell death . In another colon cancer cell
[58]
and cytochrome c (cyt c) expressions, as well as the line SW480, treatment with DADS has shown to inhibit
suppression of Bcl-2 expression . DAS can also prevent migration and invasion by downregulating glycogen
[46]
the progression of colon cancer by containing the gene synthase kinase (GSK)3β/NF-κB and LIM kinase-1
expression and activities of arylamine N-acetyltransferase (LIMK-1)/dextrin/cofilin cascades, resulting in the
and downregulating ERK1/2 pathway . In a leukemia suppression of vimentin, Ki-67, and CD-34 expressions
[47]
model, DAS restored the elevated levels of P-glycoprotein and the elevation of E-cadherin . Other signaling
[59]
(P-gp), a multidrug protein . The treatment of cervical markers targeted with DADS treatment in colon cancer
[48]
cancer cells with DAS has been reported to promote cell cells include the elevation of Ca levels, phosphorylation
2+
cycle arrest and apoptosis by increasing ROS, calcium ions of ERK, activation of STAT-1, and inhibition of Rac1/
[60]
2+
(Ca ), and the number of cells accumulated in the gap 0 PAK1/LIMK1/cofilin pathways .
(G0)/G1 phase . The treatment increases the expressions In leukemia, DADS induces cell death through the
[49]
of p21, p27, p53, Bad, Bid, Bax, apoptosis-inducing factor inhibition of Rac1/ROCK1/LIMK1/cofilin and ERK
(AIF), caspases, and cyt c but decreases the expressions of pathways as well as the activation of p38MAPK, Rac2/
Bcl-xl, Bcl-2, cyclin-dependent kinase 2 (CDK2), CDK6, JNK, and caspase-dependent apoptotic pathways . Its
[61]
checkpoint kinase (CHK)2, and human papillomavirus anticancer effects in leukemia cells are evident through
(HPV) oncogenes E6 and E7 . the downregulation of vascular endothelial growth factor
[50]
Furthermore, treating neuroblastoma cells SH-SY5Y (VEGF) and calreticulin. It inactivates epidermal growth
with DAS has been shown to suppress pro-proliferative factor receptor (EGFR) and mTOR pathways that mediate
activities and trigger apoptosis by increasing caspases the induction of G2/M and G0/G1 arrest through the
activation and Ca levels while suppressing NF-κB downregulation of PARK-7, cofilin 1, and Rho GDP
2+
[62]
pathway . In a mice lung cancer model, DAS significantly dissociation inhibitor 2 .
[51]
reduced tumor growth and increased antioxidant levels In a mice prostate cancer model, testosterone and
and apoptotic activities by suppressing the expression of N-methyl N-nitroso urea-induced cancer and its
fatty acid synthase . In a recent study, the combination of associated features such as dysplasia, hyperplasia, and
[52]
paclitaxel and DAS has been demonstrated to improve skill prostatic intraepithelial neoplasia were significantly
texture and downregulate antiapoptotic protein Bcl-2 in a reduced with DADS treatment . In addition, it has also
[63]
mice skin cancer model . been reported that DADS treatment can promote apoptosis
[53]
Alternatively, in esophageal carcinoma, a previous study through G2/M arrest due to decreased CDK1 expression
has revealed that DAS is only effective when administered and the activation and inhibition of JNK and PI3K/AKT
after its exposure to carcinogen, which suggests that the pathways, respectively. Furthermore, DADS also initiates
compound is more effective as a treatment rather than for histone hyperacetylation, increasing DNA damage,
prevention purposes [54,55] . Overall, DAS has considerable raising the expression of pro-apoptotic cell markers, and
[64]
potential as a therapeutic option for cancer. However, further decreasing migration and invasion-associated proteins .
studies are required to shed light on the possible ways of In hepatocellular carcinoma (HCC), DADS has been
improving its efficiency and reducing the side effects. reported to reduce cell proliferation and migration by
promoting apoptosis by regulating associated markers and
2.1.4. Diallyl disulfide (DADS) G2/M arrest. Moreover, it also been reported to induce
DADS is an organosulfur compound from garlic with antiapoptotic activities and reduce toxicity by inhibiting
[65]
strong anticancer properties. It is formed from allicin. CYP2E1 . Albeit, the pro-apoptotic effects of DADS can
DADS has demonstrated its effects in different types of be increased in HCC by cotreating with other compounds,
[66]
cancers through the regulation of apoptosis, oxidative such as p38 or p42/44 MAPK inhibitors .
stress, and cell cycle, along with several cellular pathways DADS enhances programmed cell death in breast cancer
associated with cancer survival and progression . by promoting G0 arrest, altering Bcl-2 family proteins,
[56]
For example, in colon cancer cells HT-29 and Caco-2, inhibiting HDAC through histone-4 hyperacetylation,
treatment with DADS has shown to induce anticancer suppressing ERK, and activating SAPK/JNK and p38MAPK
effects by activating histone 3, inhibiting histone pathways . The inhibition of ERK by DADS in breast
[67]
deacetylase (HDAC), and increasing p21 expression . cancer is initiated through the upregulation of miR-34a
[57]
In HCT-116, DADS has been shown to trigger G2/M expression, leading to the inhibition of upstream cascades,

Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/gpd.v2i1.164