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      Observing hydrogen sulfide in the endoplasmic reticulum of cancer cells and zebrafish by using an activity-based fluorescent probe

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          Abstract

          Hydrogen sulfide (H 2S) in the endoplasmic reticulum of living systems could be imaged using probe ER-Nap-NBD.

          Abstract

          A crucial endogenous signaling chemical, hydrogen sulfide, is involved in many physiological actions. In this work, we created the fluorescent probe ER-Nap-NBD using a naphthalimide fluorophore as the signal reporter, a 7-nitro-1,2,3-benzoxadiazole amine as the responsive moiety, and a sulfonamide part for endoplasmic reticulum targeting. ER-Nap-NBD could be detected the H 2S levels in solution and in living systems (cells and zebrafish).

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          A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

          Xu Cao, Lei Ding, Zhi-zhong Xie … (2019)
          Significance: Hydrogen sulfide (H2S) has been recognized as the third gaseous transmitter alongside nitric oxide and carbon monoxide. In the past decade, numerous studies have demonstrated an active role of H2S in the context of cancer biology. Recent Advances: The three H2S-producing enzymes, namely cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), have been found to be highly expressed in numerous types of cancer. Moreover, inhibition of CBS has shown anti-tumor activity, particularly in colon cancer, ovarian cancer, and breast cancer, whereas the consequence of CSE or 3MST inhibition remains largely unexplored in cancer cells. Intriguingly, H2S donation at high amounts or a long time duration has also been observed to induce cancer cell apoptosis in vitro and in vivo while sparing noncancerous fibroblast cells. Therefore, a bell-shaped model has been proposed to explain the role of H2S in cancer development. Specifically, endogenous H2S or a relatively low level of exogenous H2S may exhibit a pro-cancer effect, whereas exposure to H2S at a higher amount or for a long period may lead to cancer cell death. This indicates that inhibition of H2S biosynthesis and H2S supplementation serve as two distinct ways for cancer treatment. This paradoxical role of H2S has stimulated the enthusiasm for the development of novel CBS inhibitors, H2S donors, and H2S-releasing hybrids. Critical Issues: A clear relationship between H2S level and cancer progression remains lacking. The possibility that the altered levels of these byproducts have influenced the cell viability of cancer cells has not been excluded in previous studies when modulating H2S producing enzymes. Future Directions: The consequence of CSE or 3MST inhibition in cancer cells need to be examined in the future. Better portrayal of the crosstalk among these gaseous transmitters may not only lead to an in-depth understanding of cancer progression but also shed light on novel strategies for cancer therapy.
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            Hydrogen sulfide chemical biology: pathophysiological roles and detection.

            Gopi Kolluru, Christopher G. Kevil, Xinggui Shen … (2013)
            Hydrogen sulfide (H2S) is the most recent endogenous gasotransmitter that has been reported to serve many physiological and pathological functions in different tissues. Studies over the past decade have revealed that H2S can be synthesized through numerous pathways and its bioavailability regulated through its conversion into different biochemical forms. H2S exerts its biological effects in various manners including redox regulation of protein and small molecular weight thiols, polysulfides, thiosulfate/sulfite, iron-sulfur cluster proteins, and anti-oxidant properties that affect multiple cellular and molecular responses. However, precise measurement of H2S bioavailability and its associated biochemical and pathophysiological roles remains less well understood. In this review, we discuss recent understanding of H2S chemical biology, its relationship to tissue pathophysiological responses and possible therapeutic uses. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Aminopeptidase N Activatable Fluorescent Probe for Tracking Metastatic Cancer and Image-Guided Surgery via in Situ Spraying.

              Haidong Li, Qichao Yao, Wen Sun … (2020)
              The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).
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                Author and article information

                Contributors
                Journal
                Journal ID (publisher-id): CHCOFS
                Title: Chemical Communications
                Abbreviated Title: Chem. Commun.
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 1359-7345
                ISSN (Electronic): 1364-548X
                Publication date Created: February 23 2023
                Publication date (Electronic): 2023
                Volume: 59
                Issue: 17
                Pages: 2493-2496
                Affiliations
                [1 ]State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China
                [2 ]School of Bioengineering, Dalian University of Technology, 2 Linggong Road, 116024, Dalian, Liaoning, China
                [3 ]Department of Chemistry and Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Korea
                [4 ]Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058, Basel, Switzerland
                Article
                DOI: 10.1039/D2CC06645A
                SO-VID: 16d4d14d-391d-41e4-b435-5f9e2945b933
                Copyright © © 2023
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                http://rsc.li/journals-terms-of-use

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