Characterization of Hydrogen Sulfide and Its Synthases, Cystathionine β-Synthase and Cystathionine γ-Lyase, in Human Prostatic Tissue and Cells

Guo, Hui; Gai, Junwei; Wang, Ying; Jin, Hang; Du, Junbao; Jin, Jie

doi:10.1016/j.urology.2011.10.013

Cited by 84 publications

(76 citation statements)

References 13 publications

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“…The protein expression and activity of H 2 S-forming enzymes, CSE and CBS, in the prostate cancer LNCaP cells are much more than those in normal prostatic epithelial RWPE-1 cells [64] . The expression of these enzymes in LNCaP cells increases during neuroendocrinelike differentiation induced by treatment with db-cAMP plus isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor [17] .…”

Section: The H 2 S/ca V 32 Pathway Regulates Neuroendocrine Secretiomentioning

confidence: 88%

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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Background: Hydrogen sulfide (H₂S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H₂S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Ca_v3.2 T-type Ca²⁺ channels mediate some of the biological activity of H₂S, we focus on the role of the H₂S/Ca_v3.2 pathway in regulating the neuronal and neuroendocrine function. Summary: In the neuronal system, H₂S regulates the activity of various ion channels including Ca_v3.2. Exogenous and endogenous H₂S enhances the Ca_v3.2 channel activity, promoting somatic and visceral pain signaling. The H₂S/Ca_v3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H₂S formed by CSE regulates secretory function by enhancing Ca_v3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H₂S/Ca_v3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.

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Section: The H 2 S/ca V 32 Pathway Regulates Neuroendocrine Secretiomentioning

confidence: 88%

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Fukami

Sekiguchi²,

Kawabata³

2016

Pharmacology

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“…In addition, several prior studies demonstrated an increase in CBS expression in various forms of human cancer (33)(34)(35), although the functional consequence of these observations remained unclear. Finally, a prior Fig.…”

Section: Discussionmentioning

confidence: 99%

Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer

Szabó¹,

Coletta²,

Chao³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

608

687

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The physiological functions of hydrogen sulfide (H 2 S) include vasorelaxation, stimulation of cellular bioenergetics, and promotion of angiogenesis. Analysis of human colon cancer biopsies and patient-matched normal margin mucosa revealed the selective upregulation of the H 2 S-producing enzyme cystathionine-β-synthase (CBS) in colon cancer, resulting in an increased rate of H 2 S production. Similarly, colon cancer-derived epithelial cell lines (HCT116, HT-29, LoVo) exhibited selective CBS up-regulation and increased H 2 S production, compared with the nonmalignant colonic mucosa cells, NCM356. CBS localized to the cytosol, as well as the mitochondrial outer membrane. ShRNA-mediated silencing of CBS or its pharmacological inhibition with aminooxyacetic acid reduced HCT116 cell proliferation, migration, and invasion; reduced endothelial cell migration in tumor/endothelial cell cocultures; and suppressed mitochondrial function (oxygen consumption, ATP turnover, and respiratory reserve capacity), as well as glycolysis. Treatment of nude mice with aminooxyacetic acid attenuated the growth of patientderived colon cancer xenografts and reduced tumor blood flow. Similarly, CBS silencing of the tumor cells decreased xenograft growth and suppressed neovessel density, suggesting a role for endogenous H 2 S in tumor angiogenesis. In contrast to CBS, silencing of cystathionine-γ-lyase (the expression of which was unchanged in colon cancer) did not affect tumor growth or bioenergetics. In conclusion, H 2 S produced from CBS serves to (i) maintain colon cancer cellular bioenergetics, thereby supporting tumor growth and proliferation, and (ii) promote angiogenesis and vasorelaxation, consequently providing the tumor with blood and nutritients. The current findings identify CBS-derived H 2 S as a tumor growth factor and anticancer drug target.

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“…In an expression profiling survey, conducted in 2005, most cell lines of the NCI60 collection of human cancer cell exhibited increased CBS expression (assessed by Western blot analysis), with the highest expression levels noted in breast, ovarian, and renal cancer lines (146). In a more recent study, the prostate cancer cell lines LNCaP, PBH-1, and DU145 showed a marked increase in CBS expression, which correlated with increased H 2 S production (39).…”

Section: Increased Expression Of Cbs And/or Increased Production Of Hmentioning

confidence: 99%

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

Hellmich

Coletta

Chao

et al. 2015

Antioxidants & Redox Signaling

198

184

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Significance: Cancer represents a major socioeconomic problem; there is a significant need for novel therapeutic approaches targeting tumor-specific pathways. Recent Advances: In colorectal and ovarian cancers, an increase in the intratumor production of hydrogen sulfide (H 2 S) from cystathionine b-synthase (CBS) plays an important role in promoting the cellular bioenergetics, proliferation, and migration of cancer cells. It also stimulates peritumor angiogenesis inhibition or genetic silencing of CBS exerts antitumor effects both in vitro and in vivo, and potentiates the antitumor efficacy of anticancer therapeutics. Critical Issues: Recently published studies are reviewed, implicating CBS overexpression and H 2 S overproduction in tumor cells as a tumorgrowth promoting ''bioenergetic fuel'' and ''survival factor,'' followed by an overview of the experimental evidence demonstrating the anticancer effect of CBS inhibition. Next, the current state of the art of pharmacological CBS inhibitors is reviewed, with special reference to the complex pharmacological actions of aminooxyacetic acid. Finally, new experimental evidence is presented to reconcile a controversy in the literature regarding the effects of H 2 S donor on cancer cell proliferation and survival. Future Directions: From a basic science standpoint, future directions in the field include the delineation of the molecular mechanism of CBS upregulation of cancer cells and the delineation of the interactions of H 2 S with other intracellular pathways of cancer cell metabolism and proliferation. From the translational science standpoint, future directions include the translation of the recently emerging roles of H 2 S in cancer into human diagnostic and therapeutic approaches. Antioxid. Redox Signal. 22,

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Characterization of Hydrogen Sulfide and Its Synthases, Cystathionine β-Synthase and Cystathionine γ-Lyase, in Human Prostatic Tissue and Cells

Cited by 84 publications

References 13 publications

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Hydrogen Sulfide and T-Type Ca<sup>2+</sup> Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion

Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

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