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

Figure 2. A schematic diagram of the signaling pathways involved in the apoptosis-induction effect of DATS exposure. DATS: Diallyl trisulfide, ROS:
Reactive oxygen species, JNK: c-Jun N-terminal kinase, AP-1: Activator protein-1, ERK: Extracellular signal-regulated kinases, Bcl-2: B-cell lymphoma-2,
Bax: Bcl-2-associated X protein, AKT/PKB: Protein kinase B, PARP: Poly-ADP-ribose polymerase.

deactivation, and cyclooxygenase (COX)-2 suppression that SFN treatment can also suppress the proliferation and
through the elevation of p38 expression and activities. In metastasis of colon cancer by promoting Nrf2 expression
addition, by downregulating COX-2 and upregulating through demethylation of its promoter, upregulating
miR-200c, SFN suppresses several EMT markers, including NmrA-like redox sensor 2, pseudogene and pseudogene
MMP-2, -9, Snail, and zinc-finger E-box-binding homeobox activating ROS/p38 axis, and downregulating COX-2/
1 [104] . In recent studies, SFN has been shown to prevent the microsomal prostaglandin E synthase-1 cascades as well as
progression of bladder cancer by regulating the composition HDAC, hTERT, and miR-21 expressions. SFN also induces
of gut bacteria and protecting the gut barrier, increasing the downregulation of pro-inflammatory markers in colon
the expression of FAT atypical cadherin [105] , as well as cancer cells [108,109] .
downregulating HIF-1α expression and activities, thereby
reducing glycolysis. The chemoresistance against everolimus, In breast cancer, SFN has been reported to prevent
an mTOR inhibitor, and the upregulation of integrins α6, αV, cell progression through the upregulation of early growth
and β1 in bladder cancer can be prevented by cotreatment with response 1 and thioredoxin reductase 1 expression and
SFN [106] . In colon cancer, SFN promotes apoptotic activities redox status, a reduction in the phosphorylation of AKT and
by arresting cells at G1 and inhibiting ERK1/2 and AKT S6K1 kinases, and a suppression in the expression of SERTA
kinases, activating caspase-3 and chromatin condensation, domain containing 1, cyclin D2, and HDAC 3, resulting in
upregulating p27 through S-phase kinase-associated protein G1/S arrest [110] . In addition, the treatment of TNBC stem cells
inhibition, phosphorylating stress-activated protein kinase with SFN promotes cell death by inhibiting the expressions
and suppressing C-MYC, overexpressing p21 and inducing of Nanog, aldehyde dehydrogenase 1A1, Wnt3, Notch 4,
G2/M arrest, activating MAPK pathways, suppressing and Crypto/Alk4 protein complex formation [111] . Moreover,
HIF-1α and VEGF expressions, as well as increasing ROS in the treatment of gastric cancer with SFN, the compound
generation [107] . Moreover, further studies have indicated inhibits the progression of cancer by mediating the induction

Volume 2 Issue 1 (2023) 8 https://doi.org/10.36922/gpd.v2i1.164