Garlic-derived compound -allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway.
10.1016/j.apsb.2017.10.003
- Author:
Jia XIAO
1
;
Feiyue XING
2
;
Yingxia LIU
1
;
Yi LV
2
;
Xiaogang WANG
3
;
Ming-Tat LING
4
;
Hao GAO
5
;
Songying OUYANG
6
;
Min YANG
1
;
Jiang ZHU
7
;
Yu XIA
2
;
Kwok-Fai SO
8
;
George L TIPOE
9
Author Information
1. State Key Discipline of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen 518112, China.
2. Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
3. Department of Cell Biology & Institute of Biomedicine, Jinan University, Guangzhou 510632, China.
4. Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
5. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China.
6. Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China.
7. JM Medical (Shenzhen), LLC, Shenzhen 518112, China.
8. GMH Institute of Central Nervous System Regeneration, Jinan University, Guangzhou 510632, China.
9. School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
- Publication Type:Journal Article
- Keywords:
Axin1, axis inhibition protein 1;
DKK-1, Dickkopf Wnt signaling pathway inhibitor 1;
DVL2, disheveled 2;
FADD, Fas-associated protein with death domain;
HCC;
HCC, hepatocellular carcinoma;
Human;
KD, knock-down;
LDH, lactate dehydrogenase;
LRP6;
LRP6, low-density lipoprotein receptor (LDLR)-related protein 6;
MCL-1, myeloid cell leukemin-1;
NAFLD, non-alcoholic fatty liver disease;
Nude mice;
PCNA, proliferating cell nuclear antigen;
S-allylmercaptocysteine;
SAC, S-allylcysteine;
SAMC, S-allylmercaptocysteine;
SPR, surface plasmon resonance;
TCF/LEF, T-cell factor/lymphoid enhancing factor;
TSA, thermal shift assay;
Tm, melting temperature;
Wnt
- From:
Acta Pharmaceutica Sinica B
2018;8(4):575-586
- CountryChina
- Language:English
-
Abstract:
Whether and how garlic-derived -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.
