Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway

Chien-Yi Ho; Dai-Wei Hu; Bo-Rong Chen; Chun-Chun Yang; Chun-Hsu Yao; Tien Ni; Wei-Chuan Ho; Yueh-Sheng Chen; Chih-Yen Tu; Wei-Chao Chang; Yang-Chang Wu; Chih-Hsin Tang; Hui-Chi Huang; Wei-Chien Huang; Tzong-Shiun Li

doi:10.21873/anticanres.15542

Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway

Anticancer Res. 2022 Feb;42(2):845-855. doi: 10.21873/anticanres.15542.

Authors

Chien-Yi Ho^{1

2

3

4}, Dai-Wei Hu^{5

6}, Bo-Rong Chen^{5

6

7

8}, Chun-Chun Yang⁸, Chun-Hsu Yao^{1

9

10}, Tien Ni^{11

12}, Wei-Chuan Ho^{1

2

3

4}, Yueh-Sheng Chen^{1

9

10}, Chih-Yen Tu^{7

13}, Wei-Chao Chang⁶, Yang-Chang Wu^{14

15

16}, Chih-Hsin Tang^{5

7}, Hui-Chi Huang¹⁷, Wei-Chien Huang^{18

6

19

20}, Tzong-Shiun Li^{21

22}

Affiliations

¹ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, R.O.C.
² Division of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan, R.O.C.
³ Physical Examination Center, China Medical University Hsinchu Hospital, Hsinchu, Taiwan, R.O.C.
⁴ Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan, R.O.C.
⁵ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan, R.O.C.
⁶ Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
⁷ School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
⁸ National Taichung First Senior High School, Taichung, Taiwan, R.O.C.
⁹ Biomaterials Translational Research Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
¹⁰ Department of Bioinformatics and Medical Engineering, Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan, R.O.C.
¹¹ Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
¹² Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, R.O.C.
¹³ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
¹⁴ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan, R.O.C.
¹⁵ Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
¹⁶ Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan, R.O.C.
¹⁷ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, R.O.C.; hchuang@mail.cmu.edu.tw.
¹⁸ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan, R.O.C.; whuang@mail.cmu.edu.tw.
¹⁹ Drug Development Center, China Medical University, Taichung, Taiwan, R.O.C.
²⁰ Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan, R.O.C.
²¹ Department of Plastic Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.; li.tsa2@icloud.com.
²² Innovation Research Center, Show Chwan Health Care System, Changhua, Taiwan, R.O.C.

PMID: 35093882
DOI: 10.21873/anticanres.15542

Abstract

Background/aim: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity.

Materials and methods: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis.

Results: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus.

Conclusion: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.

Keywords: Snail mucus; TNBC; anti-cancer; apoptosis; chemotherapy.

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Doxorubicin / pharmacology
Drug Resistance, Neoplasm / drug effects
Drug Synergism
Humans
Mucus* / chemistry
Mucus* / metabolism
Signal Transduction / drug effects*
Snails* / metabolism
Triple Negative Breast Neoplasms / drug therapy
Triple Negative Breast Neoplasms / metabolism*
Triple Negative Breast Neoplasms / pathology
fas Receptor / metabolism*

Substances

Antineoplastic Agents
FAS protein, human
fas Receptor
Doxorubicin