HQS-3, a newly synthesized flavonoid, possesses potent anti-tumor effect in vivo and in vitro.

Abstract

HQS-3 is a newly baicalein derivative with a benzene substitution. We investigated the anticancer effect of HQS-3 in vivo and in vitro. HQS-3 significantly decreased tumor growth in mice inoculated with Heps and HepG2 cells; and had little influence on the state and weight of animals. After treatment with 20 mg/kg HQS-3, the inhibitory rate of tumor weight in mice inoculated with Heps and HepG2 cells were 63.62% and 68.03%, respectively. Meanwhile, HQS-3 inhibited the viability of various kinds of tumor cells with IC50 values in the range of 22.98-54.32 μM after 48 h treatment measured by MTT-assay. HQS-3 remarkably inhibited viability of hepatoma cells in a concentration- and time-dependent manner and induced apoptosis in HepG2 cells by DAPI staining and Annexin V/PI double staining. The apoptosis-induction effect of HQS-3 was attributed to its ability to modulate the activity of caspase-9, caspase-3 and PARP. Moreover, the expression of bax protein was increased while the bcl-2 protein was decreased, leading to an increase in Bax/Bcl-2 ratio. The accumulation of ROS induced by HQS-3 in HepG2 cells was also observed. The further results suggested that HQS-3 induced mitochondrial-mediated apoptosis by increasing ROS level and inhibiting the expression of anti-oxidative protein SOD2. HQS-3 exerted anti-tumor activity both in vitro and in vivo via inducing tumor cells apoptosis, and these results suggested that it deserves further investigation as a novel chemotherapy for human tumors.

• Authors: Yuxin Zhou, Na Lu, Haiwei Zhang, Libin Wei, Lei Tao, Qinsheng Dai, Li Zhao, Biqi Lin, Qilong Ding, Qinglong Guo
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 49 Issue 4 Pg. 649-58 (Jul 16 2013) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 23619285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• 7-(benzyloxy)-6-(3-(dimethylamino)-propoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one
• Antineoplastic Agents
• Flavones
• Reactive Oxygen Species

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Flavones (pharmacology, therapeutic use)
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred ICR
• Mice, Nude
• Reactive Oxygen Species (metabolism)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays