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

• Published in: European journal of pharmaceutical sciences Vol. 49; no. 4; pp. 649 - 658
• Main Authors: Zhou, Yuxin, Lu, Na, Zhang, Haiwei, Wei, Libin, Tao, Lei, Dai, Qinsheng, Zhao, Li, Lin, Biqi, Ding, Qilong, Guo, Qinglong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.07.2013
• Subjects: Animals; Anti-tumor; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Bax/Bcl-2; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Survival - drug effects; Flavones - pharmacology; Flavones - therapeutic use; HQS-3; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Inbred ICR; Mice, Nude; Mitochondrial-mediated; Reactive Oxygen Species - metabolism; ROS; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; Mitochondrial-mediated; Anti-tumor; Bax/Bcl-2; HQS-3; ROS; Apoptosis
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.04.016

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 20mg/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 22.98–54.32μM after 48h 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.