Arsenic trioxide inhibits the growth of A498 renal cell carcinoma cells via cell cycle arrest or apoptosis.

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Hyun Park W, Hee Cho Y, Won Jung C, Oh Park J, Kim K, Hyuck Im Y, Lee MH, Ki Kang W, Park K

Arsenic trioxide inhibits the growth of A498 renal cell carcinoma cells via cell cycle arrest or apoptosis.

Biochem Biophys Res Commun. 2003 Jan 3;300(1):230-5.

PubMed ID

12480548 [ View in PubMed

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Abstract

Previously, we showed that arsenic trioxide potently inhibited the growth of myeloma cells and head and neck cancer cells. Here, we demonstrate that arsenic trioxide inhibited the proliferation of all the renal cell carcinoma cell lines (ACHN, A498, Caki-2, Cos-7, and Renca) except only one cell line (Caki-1) with IC(50) of about 2.5-10 microM. Arsenic trioxide induced a G(1) or a G(2)-M phase arrest in these cells. When we examined the effects of this drug on A498 cells, arsenic trioxide (2.5 microM) decreased the levels of CDK2, CDK6, cyclin D1, cyclin E, and cyclin A proteins. Although p21 protein was not increased by arsenic trioxide, this drug markedly enhanced the binding of p21 with CDK2. In addition, the activities of CDK2- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Arsenic trioxide (10 microM) also induced apoptosis in A498 cells. Apoptotic process of A498 cells was associated with the changes of Bcl-(XL), caspase-9, caspase-3, and caspase-7 proteins as well as mitochondria transmembrane potential (Deltapsi(m)) loss. Taken together, these results demonstrate that arsenic trioxide inhibits the growth of renal cell carcinoma cells via cell cycle arrest or apoptosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Arsenic trioxide	G1/S-specific cyclin-D1	Protein	Humans	Yes	Antagonist	Details

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Arsenic trioxide	Approved Investigational	BCL2L1	598	decreased	arsenic trioxide results in decreased expression of BCL2L1 protein	20q11.21