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

SRC and Ras . Similarly, other studies have shown that progression of cancer by regulating cell cycle, apoptosis,
[68]
DADS treatment can reduce breast cancer progression and and oxidative stress events by promoting the activation of
metastases by elevating the expressions of tristetraprolin . p53- and p21-mediated Nrf2 . In brain tumors, treatment
[68]
[42]
Furthermore, the investigation of normal breast cancer with DADS can effectively reduce p38 MAPK, NF-κB, and
cells MCF-10A has indicated that DADS pre-treatment H-RAS expressions, increase peroxisome proliferator-
can protect against benzo(a)pyrene-induced cancer and activated receptor-gamma coactivator-1α and Ca levels,
2+
the compound can help to avert environmentally induced trigger G2/M arrest, and activate JNK/c-Jun pathways
cancer initiation . It has also been demonstrated that and mitochondria-dependent apoptosis, which ultimately
[69]
DADS treatment can effectively inhibit pro-cancer activities result in tumor suppression .
[79]
in triple-negative breast cancer (TNBC) cells by suppressing Furthermore, in the treatment of cervical cancer
antiapoptotic proteins and β-catenin activation . In with DADS, the compound inhibits cell proliferation by
[70]
addition, nanoemulsions of DADS with α-linolenic acid targeting TAp73/ΔNp73 status and activating p53/p21
can trigger G0/G1 arrest and regulate the ERK pathway in [80]
MCF-7 cells . Moreover, the modification of DADS loaded signaling pathways . DADS induces its anticancer effects
[71]
in bladder cancer by inhibiting N-acetyl transferase (NAT)
in solid-lipid nanoparticles with receptor for advanced activities as well as promoting ROS production and G2/M
glycation end products antibody improves the efficiency of arrest . Besides, the inhibitory effects of DADS have
[81]
DADS by facilitating target-specific delivery and reducing been reported in other types of cancers, including the
off-target effects in TNBC .
[72]
suppression of EMT through MAPK/ERK inactivation
DADS exerts its anticancer effects in lung cancer by in oral cancer, G2/M arrest in pancreatic cancer, G1/S
regulating the expression of apoptotic proteins, increasing arrest associated with MAPK phosphorylation in
ROS levels, and Ca elevation, inducing G2/M arrest, nasopharyngeal carcinoma, the upregulation of miR-34
2+
and activating p53, p42/44MAPK, and JNK pathways . and p21 expressions and inactivation of PI3K/AKT/mTOR
[73]
Cisplatin-resistant lung cancer cells A549/DPP can be in osteosarcoma , as well as C-MYC, specificity protein
[82]
sensitized to DADS by cotreating with small interfering 1 (SP1), and MAD1-mediated attenuation of human
(si)RNA BCL-2 . In a recent study, DADS has been telomerase reverse transcriptase (hTERT) in lymphoma.
[74]
shown to prevent cancer growth and EMT in A549 cells Overall, the role of DADS in cancer has been extensively
by suppressing E-cadherin and cytokeratin-18 as well as studied, and numerous pathways have been implicated in
elevating N-cadherin and vimentin through inactivating the process. However, the research on the side effects of
Wingless and Int-1 (Wnt)/β-catenin pathway . the drug and its elimination mechanisms is still lacking,
[75]
Moreover, the treatment of esophageal carcinoma thereby requiring further investigations.
models with DADS has been reported to cause cell death 2.1.5. Diallyl trisulfide (DATS)
through the suppression of NAT and CYP2E1 expressions,
the activation of mitochondria-apoptosis and p53/p21 Similar to DAS and DADS, DATS is an organic compound
pathways, and the inhibition of Raf/mitogen-activated produced by garlic. It has immense therapeutic significance
protein kinase kinase (MEK)/ERK pathway . in different types of cancers. Dose combination also affects
[76]
various cellular processes, including cell cycle, apoptosis,
In a recent study, DADS has also been shown to prevent
the metastasis of type 2 esophageal-gastric junction proliferation, EMT, and oxidative stress. Numerous in vitro
and in vivo studies of different types of cancers have been
adenocarcinoma cells by decreasing the expression of conducted to investigate the drug’s potential for therapeutic
matrix metalloproteinases (MMPs) and increasing the purposes. In prostate cancer models, DATS treatment has
expression of MMP tissue inhibitors partly through
[55]
the inactivation of NF-κB and PI3K/AKT pathways . been shown to promote a decrease in the expression of
Furthermore, DADS inhibits the cell cycle. DADS promotes X-linked inhibitor of apoptosis protein (XIAP), an increase
in pro-apoptotic protein Bak, JNK1-mediated activation of
ROS production, causes DNA damage, upregulates miR- ITCH ubiquitin ligase signaling axis, JNK1/2 and ERK1/2
34a, miR-22, and miR-200b expressions, as well as inhibits activation; AKT, NF-κB, and p-STAT-3 inhibition; as well
PI3K/AKT and Wnt/β-catenin cascades . However, a
[77]
possible resistance to DADS by gastric cancer cells has as G2/M arrest due to CHK1 activation and increase in p53
[82,83]
been found to be associated with the increase in GSH and p-Cdc25C expressions .
peroxidase or GSH levels, resulting in the alteration of In breast cancer, DATS treatment suppresses the
ROS status. This suggests that the compound may not be expressions of Bcl-2, Bcl-xL, MMP-2, estrogen receptor
fully efficient in treating this type of cancer . Studies on (ER)-α, lactate dehydrogenase-A (LDHA), Forkhead
[78]
skin cancer have demonstrated that DADS can prevent the box Q1 (FOXQ1), hypoxia-inducible factor (HIF)-α, and

Volume 2 Issue 1 (2023) 6 https://doi.org/10.36922/gpd.v2i1.164