Hydrogen Sulfide Used in Cancer Treatment

Hydrogen sulfide is usually a highly toxic gas. However, with careful preparation, it can be used to support photothermal therapy (PTT) intreating cancer, as a team of researchers reporting in the journal Angewandte Chemie has recently discovered. As the team reports, an adjuvant releasinghydrogen sulfide causes tumor cells to lose their natural heatprotection and thus to become significantly more sensitive to PTT.

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Breathing in gaseous hydrogen sulfide usually causes us to suffocate, because the gas suppresses the respiratory chain in the mitochondria,the power houses of the cells. However, molecular hydrogen sulfide, when delivered in small amounts to cells, is not entirely toxic. Instead, it also acts as a messenger molecule and plays a role in cancer cellgrowth. With this in mind, a team of researchers working with Xiaoyuan(Shawn) Chen of the National University of Singapore, focused on theeffects of hydrogen sulfide in the heat protection mechanisms of tumorcells.

The team chose this angle because tumor cells have the ability toprotect themselves against excessive heat. In essence, the aim ofphotothermal therapy is to "boil" cancer cells from the inside out. Toreach the required temperatures, a photosensitizer introduced into thecells converts incoming laser light into heat. However, tumor cellsrespond to this heat attack by increasing production of heat shockproteins (HSP), reducing the efficacy of the treatment.

To make their HSPs, however, the cell needs energy equivalentsproduced in the mitochondrial respiratory chain, and it is here thatChen and the team intervened. They discovered that hydrogen sulfide,when released into tumor cells in appropriate amounts, disruptsmitochondrial respiration, suppresses HSP production, and makes it moredifficult for tumor cells to protect themselves. As a hydrogen sulfidedonor, the team chose FDA-approved anethole trithione-a drug originallyused as a treatment for dry mouth and to stimulate bile secretion, butalso known for its ability to continually release hydrogen sulfide whenbroken down in the cell.

To complete photothermal therapy, the team coupled an anetholetrithione derivative with copper sulfide nanodiscs, which are used inPTT as a photosensitizer to efficiently convert near-infrared light into heat. A single-dose treatment led to the eradication of tumors inlaboratory mice, which had been previously implanted with breast tumors, within only a few days. Chen and the team also found that they couldperform the PTT at lower temperatures using the adjuvant-photosensitizer combination, limiting damage to surrounding healthy tissue. The authors suggest using this energy remodeling approach using hydrogen sulfidedonor adjuvants as a more general approach to effective PTT.

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Dr. Xiaoyuan (Shawn) Chen is a Nasrat Muzayyin Chair Professor in Medicine and Technology,Yong Loo Lin School of Medicine and College of Design and Engineering,National University of Singapore. His research interests include thediagnostics and therapeutics of cancer and cardiovascular diseases with a focus on the modification of biomolecules, nanomedicine for enhancedgene and drug delivery, and ultrasensitive nanobiosensors.

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