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

upregulated in hepatoma cells SMMC-7721 and HepG2 3.3. 3-mercaptopyruvate sulfurtransferase inhibitor
but downregulated in BEL-7404 compared to normal cells 3-MPST in commonly found in cells. It regulates
HL-7702 and QSG-7701 [237] . In addition, the silencing of various cellular activities, including bioenergetics,
CBS through siRNA or pharmacological inhibitors, AOAA angiogenesis, and the mitochondria electron transport
and quinolone-indolone conjugate, effectively induced an system [265] . In an animal model of colon cancer, treatment
anticancer effect in SMMC-7721 by promoting oxidative with the 3-MPST inhibitor 2-[(4-hydroxy-6-methyl
stress and activating caspase-3.
pyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-
Besides, treatment with another inhibitor of CBS, one (HMPSNE) suppresses H S production, CT26 cells
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CH004, has also been shown to cause cell death in proliferation, migration, and oxidative phosphorylation-
HCC by promoting ferroptosis [256] . High CBS level has associated cellular bioenergetics [266] . HMPSNE treatment
been found to be associated with drug resistance in also suppresses migration- and invasion-promoting
HepG2 cells, and its inhibition increases their sensitivity markers in colon cancer cells by suppressing Wnt-β-
to doxorubicin and sunitinib; however, in BEL-7404, the catenin pathway [267] . In human breast cancer cells MCF-7,
elevation of CBS levels enhances the sensitivity to the treatment with another inhibitor, S-Allyl-L-cysteine, has
drugs [257] . This confirms that the effect of CBS in HCC is been shown to reduce cell viability by attenuating 3-MPST
cell dependent. CBS expression has also been reported expression and, subsequently, H S level [268] . On the
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to be significantly increased and associated with poor contrary, in neuroblastoma cells, the elevation of 3-MPST
prognosis in renal cancer and cholangiocarcinoma [258] , activities has shown anticancer properties [167] . The above
suggesting that the enzyme is involved in cancer evidence suggests an involvement of 3-MPST in cancer
activities. However, evidence on its inhibition is still progression; however, its precise mechanism of action,
lacking. In ovarian cancer, CBS gene silencing reduces the pathways involved, and its inhibition effect in different
migration, angiogenesis, and lipid contents [241] . The types of cancers are yet to be identified.
inhibition of CBS also activates the JNK pathway
and suppresses mitofusin, resulting in mitochondrial 4. Translation of H S research into
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morphogenesis reprogramming and the sensitization of therapeutic format
cells to erastin [259] . In a recent study, a nanoformulation
comprising selenium-containing chrysin has been The findings from the aforementioned research on H S
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shown to induce its anticancer effects in ovarian cancer donors and inhibitors show considerable potential for
cells by reducing CBS expression, thereby causing the development of H S-based chemopreventive cancer
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oxidative stress [260] . In colon cancer, CBS overexpression therapies in the near future. The research community
is associated with cancer development and treatment expects substantial outcomes from the preclinical trials
with AOAA, and CBS gene silencing can significantly on H S-based chemopreventive drugs. However, to
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reverse pro-cancer activities [261] . AOAA also sensitizes shape the future of H S research in oncology practice, it
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colon cancer cells to oxaliplatin by impairing the is highly significant to investigate the biochemistry and
antioxidant system and promoting ROS generation. pharmacology of H S donors and inhibitors as well as
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Treatment with AOAA has also been indicated to characterize their dose-dependent responses to cancer
induce the upregulation of E-cadherin and zonula cells. A huge gap remains in understanding how H S-
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occludens-1 as well as the suppression of fibronectin, producing enzymes respond to the exposure of inhibitors
thereby inhibiting the migration and invasion activities and donors in cancer cells and how they reinforce to
of colon cancer cells and promoting mesenchymal- generate signals of apoptosis and proliferation in the
epithelial transition [262] . Other CBS inhibitors that cancer microenvironment. To reach a large audience
induce apoptosis in colon cancer cells include across multiple disciplines and promote the innovation
2,3,4-trihydroxybenzylhydrazine and sikokianin C [263] . of H S biomedicine, identifying potential therapeutic H S
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Moreover, treatment with AOAA in multiple myeloma scavengers and donors are as important as assessing their
reduces cell cycle progression by triggering G0/G1 arrest biomedical applications.
and promotes apoptosis through Bcl-2 inhibition and 5. Conclusion
caspase-3 activation [264] . CBS knockdown in glioma cells
is to have a fatal outcome, as it results in the progression H S is widely recognized for its enormous diagnostic
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and metastasis of cancer. These data suggest that CBS and therapeutic advantages in various diseases,
plays a role in cancer activities in different types of cells, including cancer. Besides its involvement in other
with its effects varying accordingly; its anticancer effect pathophysiological illnesses, H S plays a significant role in
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is selective only to certain types of cancers or cells. regulating various cellular activities, such as angiogenesis,

Volume 2 Issue 1 (2023) 17 https://doi.org/10.36922/gpd.v2i1.164