Effects of hydrogen sulfide synthase CBS and CSE on malignant biological behaviour of breast cancer cells

Mengmeng ZHAO, Yalu WANG, Yuxiang XU, Kaige YANG, Yuwen CAO, Wenhu ZHOU, Jing FEI, Wen WANG, Chenghua LUO, Jianming HU

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J Jilin Univ Med Ed ›› 2025, Vol. 51 ›› Issue (1) : 34-43. DOI: 10.13481/j.1671-587X.20250105
Research in basic medicine

Effects of hydrogen sulfide synthase CBS and CSE on malignant biological behaviour of breast cancer cells

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Abstract

Objective To investigate the expressions of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) and their effects on the malignant biological behaviours of breast cancer cells, and to elucidate their mechanisms. Methods The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected, and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue, paracancerous normal tissue, MCF-7 cells, and MDA-MB-231 cells. The MCF-7 cells were divided into siNC group (transfected with siNC) and siCBS group (transfected with siCBS), and the MDA-MB-231 cells were divided into ovNC group (transfected with CSE over-expression empty plasmid) and ovCSE group (transfected with CSE over-expression plasmid). CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups, Transwell assay was used to detect the numbers of migration and invasion cells in various groups, and Western blotting method was used to detect the protein expression levels of E-cadherin, N-cadherin and Vimentin proteins in the breast cancer cells in various groups. Results Compared with paracancerous normal tissue, the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased (P<0.05 or P<0.01). Compared with MDA-MB-231 cells, the CBS mRNA expression level in the MCF-7 cells was increased (P<0.05); compared with MCF-7 cells, the expression level of CSE protein in the MDA-MB-231 cells was decreased (P<0.05). Compared with siNC group, the proliferation activity, the numbers of migration and invasion cells, the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P<0.05), and the expression level of E-cadherin protein was increased(P<0.05). Compared with ovNC group, the proliferation activity, the numbers of migratoin and invasion cells, and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased (P<0.05), while the expression level of E-cadherin protein was significantly decreased (P<0.05). Conclusion The expressions of CBS and CSE are upregulated in breast cancer tissue, and high levels of CBS and CSE promote proliferation, migration, invasion and epithelial-mesenchymal transition(EMT) of breast cancer cells.

Key words

Cystathionine-β-synthase / Cystathionine-γ-lyase / Hydrogen sulfide / Breast neoplasms / Cell proliferation / Cell migration

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Mengmeng ZHAO , Yalu WANG , Yuxiang XU , et al . Effects of hydrogen sulfide synthase CBS and CSE on malignant biological behaviour of breast cancer cells. Journal of Jilin University(Medicine Edition). 2025, 51(1): 34-43 https://doi.org/10.13481/j.1671-587X.20250105

References

1
SUNG H FERLAY J SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin202171(3): 209-249.
2
HUPPERT L A GUMUSAY O IDOSSA D, et al. Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer[J]. CA Cancer J Clin202373(5): 480-515.
3
AGOSTINETTO E GLIGOROV J PICCART M. Systemic therapy for early-stage breast cancer: learning from the past to build the future[J]. Nat Rev Clin Oncol202219(12): 763-774.
4
ZOU Y YE F KONG Y, et al. The Single-Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer[J].Adv Sci (Weinh)202210(5): 2203699.
5
POZZI G GOBBI G MASSELLI E, et al. Buffering Adaptive Immunity by Hydrogen Sulfide[J]. Cells202211(3): 325.
6
SHACKELFORD R E MOHAMMAD I Z MERAM A T, et al. Molecular Functions of Hydrogen Sulfide in Cancer[J]. Pathophysiology202128(3): 437-456.
7
YOUNESS R A ASSAL R A ABDEL MOTAAL A, et al. A novel role of sONE/NOS3/NO signaling cascade in mediating hydrogen sulphide bilateral effects on triple negative breast cancer progression[J]. Nitric Oxide201880: 12-23.
8
LI M LIU Y DENG Y, et al. Therapeutic potential of endogenous hydrogen sulfide inhibition in breast cancer (Review)[J]. Oncol Rep202145(5): 68.
9
ONKAR S S CARLETON N M LUCAS P C, et al. The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes[J]. Cancer Discov202313(1): 23-40.
10
GIUFFRÈ A TOMÉ C S FERNANDES D G F, et al. Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment[J]. Adv Exp Med Biol20201219: 335-353
11
MASI A D ASCENZI P. H2S: A“Double face”molecule in health and disease[J]. BioFactors201339(2): 186-196.
12
SZABO C COLETTA C CHAO C, et al. Tumor-derived hydrogen sulfide, produced by cystathionine-β- synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer[J]. Proc Natl Acad Sci USA2013110(30): 12474-12479.
13
WANG M YAN J CAO X, et al. Hydrogen sulfide modulates epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via HIF-1α activation[J]. Biochem Pharmacol2020172: 113775.
14
JIANG Q Y LI J M JING M R, et al. Cystathionine-β- Synthase Regulates the proliferation, migration, and invasion of thyroid carcinoma cells[J]. Oxid Med Cell Longev20222022: 8678363.
15
HELLMICH M R SZABO C. Hydrogen sulfide and cancer[J]. Handb Exp Pharmacol2015230: 233-241.
16
WANG Y HUANG J CHEN W, et al. Dysregulation of cystathionine-γ-lyase promotes prostate cancer progression and metastasis[J]. EMBO Rep201920(10): e45986.
17
PAN Y YE S YUAN D, et al. Hydrogen sulfide (H2S)/cystathionine-γ-yase (CSE) pathway contributes to the proliferation of hepatoma cells[J]. Mutat Res2014(763-764): 10-18.
18
杨钰萌, 王 新, 麻 婧. M1/M2型巨噬细胞在肝纤维化中的作用研究进展[J]. 解放军医学杂志202449(6): 726-732.
19
KALLURI R WEINBERG R A. The basics of epithelial-mesenchymal transition[J]. J Clin Invest2009119(6): 1420-1428.
20
GONZALEZ D M MEDICI D. Signaling mechanisms of the epithelial-mesenchymal transition[J]. Sci Signal20147(344). DOI: 10.1126/scisignal.2005189 .
21
PARK M KIM D, KO S, et al. Breast Cancer Metastasis: Mechanisms and Therapeutic Implications[J]. Int J Mol Sci202223(12): 6806.
22
ZHANG H SONG Y ZHOU C, et al. Blocking endogenous H2S signaling attenuated radiation-induced long-term metastasis of residual HepG2 cells through inhibition of EMT[J]. Radiat Res2018190(4): 374.
23
ASCENÇÃO K DILEK N AUGSBURGER F, et al. Pharmacological induction of mesenchymal-epithelial transition via inhibition of H2S biosynthesis and consequent suppression of ACLY activity in colon cancer cells[J]. Pharmacol Res2021165: 105393.

赵蒙蒙参与课题设计、数据整理和论文撰写,王雅璐、许宇翔和杨凯歌参与实验操作过程,曹玉文和周文虎参与论文审校,费晶参与组织样本的收集,王雯、罗成华和胡建明参与指导课题设计和论文撰写。

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