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

cellular bioenergetics, proliferation, apoptosis, EMT, Writing – review & editing: IIrum Waheed, Fatima Khan,
and autophagy, all of which are involved in cancer. The Razia Virk, Istaqlal Hussain
current understanding of H S research reveals that both
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the upregulation and downregulation of H S might have Ethics approval and consent to participate
2
anticancer effects, depending on the type of cancer. With Not applicable.
the recent advancements in science and technology,
researchers have testified that the ability of applied H S Consent for publication
2
donor or inhibitor drugs to induce their corresponding Not applicable.
effects on H S production varies, resulting in pro-cancer
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or anticancer properties of varying magnitude ranging Availability of data
from none or little to a strong influence depending on the
drug type and targeted cells. Besides the individual impact, Not applicable.
combining H S drugs with other anticancer drugs have References
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been reported to induce significant anticancer effects and
sensitize cells to treatments. 1. Mishanina TV, Libiad M, Banerjee R, 2015, Biogenesis of
reactive sulfur species for signaling by hydrogen sulfide
Furthermore, by alternating H S levels, numerous oxidation pathways. Nat Chem Biol, 11(7): 457–464.
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cellular markers that are associated with cell growth and https://doi.org/10.1038/nchembio.1834
progression have been reported to be affected, resulting in
cancer inhibition or aggravation. Despite the huge potential 2. Cao X, Ding L, Xie ZZ, et al., 2019, A review of hydrogen
of these H S-based natural, native, and designed chemicals sulfide synthesis, metabolism, and measurement: is
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in cancer treatment, little is known about the mechanism modulation of hydrogen sulfide a novel therapeutic for
of action of these drugs. To shape the future of H S cancer? Antioxid Redox Signal, 31(1): 1–38.
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research in oncology practice, conclusive investigations https://doi.org/10.1089/ars.2017.7058
are required to assess the drug concentration for treatment 3. Augsburger F, Szabo C, 2020, Potential role of the
and the specificity of both H S donors and inhibitors 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen
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before their use as candidate drugs for cancer treatment in sulfide (H2S) pathway in cancer cells. Pharmacol Res,
clinical settings. 154: 104083.

Acknowledgments https://doi.org/10.1016/j.phrs.2018.11.034
4. Shi Y, Hussain Z, Zhao Y, 2022, Promising application of
The authors thank the expert reviewers for taking time to D-amino acids toward clinical therapy. Int J Mol Sci, 23(18):
review the manuscript and provide valuable suggestions to 10794.
improve the manuscript. Hussain acknowledges and pays
countless thanks to MTB for his presence and support in https://doi.org/10.3390/ijms231810794
his PhD journey. 5. Myszkowska J, Derevenkov I, Makarov SV, et al., 2021,
Biosynthesis, quantification and genetic diseases of the
Funding smallest signaling thiol metabolite: Hydrogen sulfide.
Antioxidants (Basel), 10(7): 1065.
This work was supported by the National Natural Science
Foundation of China (Grant Nos. 31902287 and 81670088). https://doi.org/10.3390/antiox10071065
6. Kohl JB, Mellis AT, Schwarz G, 2019, Homeostatic impact
Conflict of interest of sulfite and hydrogen sulfide on cysteine catabolism. Br J

All the authors declare no conflicts of interest. Pharmacol, 176(4): 554–570.
https://doi.org/10.1111/bph.14464
Author contributions
7. Khattak S, Rauf MA, Khan NH, et al., 2022, Hydrogen sulfide
Conceptualization: Nazeer Hussain Khan, Ebenezeri Erasto biology and its role in cancer. Molecules, 27(11): 3389.
Ngowi, Dong-Dong Wu https://doi.org/10.3390/molecules27113389
Visualization: Jiebin Cao, Hongxia Liu
Supervised: Zhihui Liu, Xin-Ying Ji 8. Sun HJ, Wu ZY, Nie XW, et al., 2021, Implications of
hydrogen sulfide in liver pathophysiology: Mechanistic
Writing – original draft: Nazeer Hussain Khan, Ebenezeri insights and therapeutic potential. J Adv Res, 27: 127–135.
Erasto Ngowi, Dong-Dong Wu, Yan Li, SaadUllah
Khattak, Yingshuai Zhao, Muhammad Shahid, Ujala https://doi.org/10.1016/j.jare.2020.05.010
Zafar 9. Kumar M, Sandhir R, 2018, Hydrogen sulfide in physiological

Volume 2 Issue 1 (2023) 18 https://doi.org/10.36922/gpd.v2i1.164