NDLI: Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

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Metallomics Vol - 7 Issue - 4

Metallomics Vol - 7 Issue - 3

Metallomics Vol - 7 Issue - 2

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

Content Provider	Royal Society of Chemistry (RSC)
Author	Yuan, Jian Zhu, Feng Lei, Zhinian Wang, Xi Chen, Dongbo
Copyright Year	2015
Abstract	To evaluate the anticancer mechanism of the new ruthenium complex-Λ-WH0402 at the cellular level, the in vitro cytotoxicity of Λ-WH0402 was investigated on 10 human tumor cell lines. Λ-WH0402 was found to have higher anticancer activity than cisplatin toward human liver cancer HCCLM6 cells that have high tumor metastatic characteristics. Meanwhile, Λ-WH0402 showed an antimetastatic effect on HCCLM6 cells in vitro, mostly through its effect on cell adhesion, invasion and migration. In addition, Λ-WH0402 significantly reduced tumor metastasis to the lungs in orthotopic mouse hepatocellular cancer (HCC) models induced by HCCLM6 cells. Furthermore, Λ-WH0402 exerted an inhibitory effect on tumor cell growth and proliferation and induced dose-dependent cell cycle arrest in the S phase in HCCLM6 cells. Immunoblotting analysis showed that Λ-WH0402 not only decreased the expression of antiapoptotic protein Bcl-2 and nutrient-deprivation autophagy factor-1 (NAF-1), but also significantly increased the expression of Beclin-1 in HCCLM6 cells. More importantly, we identified that Λ-WH0402 treatment reduced the interaction between Bcl-2 and Beclin-1, and increased the expression of autophagic activation marker LC3B-II in HCCLM6 cells. On the whole, our results suggested that the anitcancer activity of Λ-WH0402 is mediated through promoting the Beclin-1-dependent autophagy pathway in HCCLM6 cells.
Starting Page	896
Ending Page	907
Page Count	12
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	7
Issue Number	5
Journal	Metallomics
DOI	10.1039/c5mt00010f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Bcl-2 BECN1 Ruthenium Cytotoxicity Hepatocellular carcinoma Metastasis Autophagy Cisplatin Protein Mouse S phase Cell adhesion Cell cycle Cancer
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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