On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity

Honda, Kazufumi; Hishiki, Takako; Yamamoto, Sohei; Yamamoto, Takehiro; Miura, Naruhisa; Kubo, Akiko; Itoh, Mai; Chen, Wei Yu; Takano, Masashi; Yoshikawa, Tomoyuki; Kasamatsu, Takahiro; Sonoda, Shinichiro; Yoshizawa, Hirotoshi; Nakamura, Seigo; Itai, Yuichiro; Shiota, Megumi; Koike, Daisuke; Naya, Masayuki; Hayakawa, Noriyo; Naito, Yoshiko; Matsuura, Tomomi; Iwaisako, Keiko; Masui, Toshihiko; Üemoto, Shinji; Nagashima, Kengo; Hashimoto, Yoshinori; Sakuma, Tomohiro; Matsubara, Osamu; Huang, Wilber; Ida, Tomoaki; Akaike, Takaaki; Masugi, Yohei; Sakamoto, Michiie; Kato, Tomoyasu; Ino, Yoshinori; Yoshida, Hiroshi; Tsuda, Hitoshi; Hiraoka, Nobuyoshi; Kabe, Yoshio; Suematsu, Makoto

doi:10.1016/j.redox.2021.101926

Cited by 20 publications

(25 citation statements)

References 40 publications

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“…Similarly, surface-enhanced Raman spectroscopy of 186 stage III or IV ovarian cancers indicated that higher CSE expression correlated with increased tumor polysulfides, tumor cisplatin resistance, and a poor prognosis. Cisplatin resistance was found to be related to polysulfide synthesis (23).…”

Section: Discussionmentioning

confidence: 99%

“…ETHE1 plays a significant role in H2S metabolism and protein polysulfide formation, suggesting that it might play a role in cancer (8)(9)(10)(11)(12)(13)(14)(15). Previously, ETHE1 was found to be increased in the sera of early lung cancer patients by protein serologic array analyses of 352 lung cancer cases, compared to 93 healthy samples, and 101 patients with benign pulmonary lesions (16).…”

Section: Discussionmentioning

confidence: 99%

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Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma

et al. 2021

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Background/Aim: Ethylmalonic encephalopathy 1 protein (ETHE1) plays an important role in sulfide catabolism and polysulfide formation. As sulfides and polysulfides have recently been identified as playing important roles in cancer, we hypothesized that ETHE1 expression would be increased in colon cancer. Materials and Methods: We used tissue microarray analysis to compare ETHE1 expression in benign colonic epithelium compared to colonic adenocarcinoma. In total, 26 benign colonic epithelial samples were compared to 122 cases of colonic adenocarcinomas. Results: Compared to benign colonic epithelium, ETHE1 expression was significantly increased (~two-fold) in colonic adenocarcinoma. Additionally, this expression increased with increasing colon cancer tumor grades. Conclusion: ETHE1 expression is increased in colon cancer compared to benign colonic epithelium. These data, combined with previous studies, suggest that ETHE1 may contribute to colon carcinogenesis by promoting tumor cell bioenergetics and polysulfide formation.Ethylmalonic encephalopathy 1 protein (ETHE1), also known as sulfur dioxygenase, is located on chromosome 19q13 and encodes a mettallo β-lactamase family enzyme containing a mononuclear iron center (1-4). Loss-of-function ETHE1 mutations are associated with ethylmalonic encephalopathy, a rare infantile autosomal recessive metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels, characterized by psychomotor regression with generalized hypotonia, evolving into tetraparesis, dystonia, and subsequent global neurological failure and death in the first decade (3-5). Patients with ethylmalonic encephalopathy exhibit lactic acidemia, elevated urine ethylmalonic and methylsuccinic acids, and low skeletal muscle mitochondrial respiratory complex IV activity (3-5).ETHE1 functions in the mitochondrial matrix oxidizing sulfides to sulfate or sulfate esters, and taurine, through the sequential actions of sulfide: quinone oxidoreductase, ETHE1, and rhodanese (6). Specifically, ETHE1 detoxifies/oxidizes hydrogen sulfide (H2S) and glutathione polysulfides (glutathione-persulfide, -trisulfide, and -tetrasulfide), but not cysteine-or homocysteine-persulfides/polysulfides (6-8). Interestingly, ETHE1 also exhibits cysteine protein polysulfidation activities. ETHE1 persulfide dioxygenase and polysulfidation activities are dependent on Cys247 polysulfidation and replacement of the Cys247 with serine ablates both enzymatic activities (8). The enzymes that synthesize H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), also function in polysulfide synthesis; suggesting that these enzymes and ETHE1 function together to regulate cellular polysulfide levels (8-10).Recently, one or more of the enzymes that synthesize H2S have been found to be increased in many different human malignancies, with one study of oral squamous cell carcinoma also showing significantly increased tumor H2S levels (11-13). Additionally, there is recent evide...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma

et al. 2021

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“…In the brain, 3-MST synthesizes H 2 S 3 , which is known to alter the activities of proteins, such as KEAP1, PTEN, and GAPDH [33,34]. CSE overexpressing human A549 carcinoma cells have high polysulfide levels, while CSE knockout cells show significantly lower levels, and recently CSE-generated polysulfides have been shown to play a role in ovarian cancer [35,36]. Additionally, enzymatic kinetic analyses have shown that polysulfides are likely products of CBS and CSE activities [34].…”

Section: H 2 S Synthesismentioning

confidence: 99%

“…Third, polysulfides are a new and exciting area of cellular biology [18]. Presently there are several papers showing a role for polysulfides in cancer [36,85]. Undoubtedly, First, many of the pharmacologic tools used in H 2 S research have flaws.…”

Section: Conclusion Issues and Future Directionsmentioning

confidence: 99%

Molecular Functions of Hydrogen Sulfide in Cancer

et al. 2021

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Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia–mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.

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“…They applied this technique to bioimaging of metabolites in a mouse syngeneic model of glioblastoma and found that endogenous polysulfide compounds could be visualized as a peak at 480 cm −1 . More recently, Honda et al used the same SERS technique to identify sulfur-containing metabolites associated with chemoresistance mechanisms of certain ovarian cancers [ 35 ]. They observed the SERS signal at 480 cm −1 in clear cell carcinoma, which suggests that polysulfides are present in the cancer tissues.…”

Section: Raman Imagingmentioning

confidence: 99%

Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules

Echizen

Hanaoka

2021

Biomolecules

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Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-Sn-S-R), hydrogen polysulfides (H2Sn), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required. Classically, sulfane sulfur compounds can be detected by cyanolysis, involving nucleophilic attack by cyanide ion to cleave the sulfur–sulfur bonds. The generated thiocyanate reacts with ferric ion, and the resulting ferric thiocyanate complex can be easily detected by absorption spectroscopy. Recent exploration of the properties of sulfane sulfur compounds as both nucleophiles and electrophiles has led to the development of various chemical techniques for detection, isolation, and bioimaging of sulfane sulfur compounds in biological samples. These include tag-switch techniques, LC-MS/MS, Raman spectroscopy, and fluorescent probes. Herein, we present an overview of the techniques available for specific detection of sulfane sulfur species in biological contexts.

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On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity

Cited by 20 publications

References 40 publications

Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma

Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma

Molecular Functions of Hydrogen Sulfide in Cancer

Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules

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