Therapeutic potential of endogenous hydrogen sulfide inhibition in breast cancer (Review)

Abstract

Hydrogen sulfide (H 2 S), the third gas signal molecule, is associated with the modulation of various physiological and pathological processes. Recent studies have reevealed that endogenous H 2 S may promote proliferation, induce angiogenesis and inhibit apoptosis, thereby stimulating oncogenesis. Conversely, decreased endogenous H 2 S release suppresses growth of various tumors including breast cancer. This observation suggests an alternative tumor therapy strategy by inhibiting H 2 S-producing enzymes to reduce the release of endogenous H 2 S. Breast cancer is the most common type of cancer in women. Due to the lack of approved targeted therapy, its recurrence and metastasis still affect its clinical treatment. In recent years, significant progress has been made in the control of breast cancer by using inhibitors on H 2 S-producing enzymes. This review summarized the roles of endogenous H 2 S-producing enzymes in breast cancer and the effects of the enzyme inhibitors on anticancer and anti-metastasis, with the aim of providing new insights for the treatment of breast cancer.

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

“…Elevated H 2 S-producing enzymes have been observed in multiple cancer types [ 45 , 57 , 64 , 94 ], and depletion of CBS or CTH activities results in the suppression of tumor growth in colon cancer [ 57 ], lung cancer [ 116 ], prostate cancer [ 45 ], and breast cancer [ 117 ]. Activation of MEK1, which belongs to the classical MAPK kinase pathways, is synonymous with cell proliferation and tumor growth [ 113 ].…”

In Situ Detection of Hydrogen Sulfide in 3D-Cultured, Live Prostate Cancer Cells Using a Paper-Integrated Analytical Device

“…In particular, increased expression of H 2 S-synthesizing enzymes such as cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) has been associated to the aggressiveness of several solid tumors [9]. In addition, the reduction of endogenous H 2 S release suppresses the growth of various tumors, including breast and prostate cancer [10]. As endogenous H 2 S can induce tumorigenesis [11], inhibitors of H 2 S-synthesizing enzymes have been developed to block the H 2 S production and have proven effective in cancer therapy [7,10,12,13].…”

“…In addition, the reduction of endogenous H 2 S release suppresses the growth of various tumors, including breast and prostate cancer [10]. As endogenous H 2 S can induce tumorigenesis [11], inhibitors of H 2 S-synthesizing enzymes have been developed to block the H 2 S production and have proven effective in cancer therapy [7,10,12,13]. Conversely, various H 2 S-releasing compounds, such as sulfide salts, diallyl disulfide, diallyl trisulfide, and other polysulfides, have been reported to inhibit the growth and metastasis of prostate cancer [14].…”

A naphthalimide-based peptide conjugate for concurrent imaging and apoptosis induction in cancer cells by utilizing endogenous hydrogen sulfide

“…These cellular events are critical regulators of growth and metastasis of tumors. [1][2][3][4][5] Malignant cells overexpress cystathionine βsynthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MST) to produce increased H 2 S that in turn promotes growth, survival and metastasis of these cells. 6,7 Several studies reported that overexpression of H 2 S producing enzymes leads to enhanced endogenous H 2 S concentration which then acts in an autocrine mode to promote proliferation, angiogenesis and bioenergetic reprogramming of the cancer cells.…”