A phase II study of arsenic trioxide (ATO) in patients with advanced hepatocellular carcinoma (HCC).

Rodgers, H.; Katta, Shilpa; Malani, Ashok K.; Willis, Marcia R.; Markowitz, AJ

doi:10.1200/jco.2010.28.15_suppl.e14686

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“…The recent phase II study of arsenic trioxide (As 2 O 3 ) in patients with advanced hepatocellular carcinoma (HCC) showed that As 2 O 3 was less active than sorafenib, an FDA approved drug for treatment of advanced HCC, and potential cardiotoxicity may hinder its further application (27). Numerous reports have demonstrated that combination treatment with As 2 O 3 and other therapeutic agents could sensitize leukaemic or solid cancer cells to As 2 O 3 -induced apoptosis and overcome drug resistance in the treatment of various haematopoietic or solid malignancies (28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

Hua¹

2011

Int J Oncol

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Abstract. Although arsenic trioxide (As 2 O 3 ) has been successfully employed in treatment of patients with APL (acute promyelocytic leukemia), the sensitivity of solid tumor cells to this treatment was much lower than APL cells. The single agent of As 2 O 3 was inefficient for treatment of hepatocellular carcinoma (HCC) in phase II trial demonstrating that new modalities of treatment with enhanced therapeutic effect are needed. In this study, we showed that oridonin, a diterpenoid isolated from traditional Chinese medicine Rabdosia rubescences, greatly potentiated apoptosis induced by As 2 O 3 in hepatocellular carcinoma cells. The synergistic pro-apoptosis effect of combination of these two drugs led to increase in intracellular reactive oxygen species (ROS) level and N-acetyl-L-cysteine (NAC), a thiolcontaining anti-oxidant, was able to completely block the effect. The combination treatment induced ROS-dependent decrease in mitochondrial membrane potential (MMP) decrease, and relocation of Bax and cytochrome C. Besides, oridonin dramatically increased the intracellular Ca 2+ overload triggered by As 2 O 3 . Furthermore, the co-treatment of oridonin and As 2 O 3 induced ROS-mediated down-regulation of Akt and XIAP, and inhibition of NF-κB activation. The two drug combination enhanced tumor suppression activity in murine HCC model compared with single agent treatment in vivo. These findings demonstrate that oridonin can sensitize hepatocellular carcinoma cells to As 2 O 3 treatment and will facilitate the optimization of As 2 O 3 therapy for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

Hua¹

2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

A phase II study of arsenic trioxide (ATO) in patients with advanced hepatocellular carcinoma (HCC).

Cited by 1 publication

References 0 publications

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

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