Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo

• Published in: Toxicology (Amsterdam) 2009-03, Vol.257 (1), p.80-85
• Main Authors: Li, Hua-Nan, Nie, Fei-Fei, Liu, Wei, Dai, Qin-Sheng, Lu, Na, Qi, Qi, Li, Zhi-Yu, You, Qi-Dong, Guo, Qing-Long
• Format: Article
• Language: English
• Subjects: Animals; Annexin A5 - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Caspase; Caspases - metabolism; Cell Proliferation - drug effects; Cell Shape - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Emergency; Female; Female genital diseases; Flavonoids - pharmacology; Gynecology. Andrology. Obstetrics; HeLa Cells; Humans; Inhibitory Concentration 50; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Nude mice; Oroxylin A; Poly(ADP-ribose) Polymerases - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Scutellaria baicalensis; Signal Transduction - drug effects; Time Factors; Toxicology; Tumors; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2008.12.011

Abstract Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. Here, we investigated the antitumor effect of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo . We found that after inoculated with the HeLa cells the mice treated with oroxylin A showed a significant decrease of tumor volumes and tumor weight compared with the control. Meanwhile, the growth inhibition of oroxylin A on HeLa cells were observed by MTT assay and the value of IC50 was 19.4 ± 0.7 μM after treatment for 48 h. Upon our previous research, the inhibition by oroxylin A might be through apoptosis. Then apoptosis induced by oroxylin A in HeLa cells was characterized by DAPI staining and Annexin V/PI double staining, and degradation of PARP (poly-ADP–ribose polymerase) was both found in HeLa cells and tumor tissue. Next, activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vivo and in vitro , including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased, which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that oroxylin A exhibited strong antitumor effect in HeLa cell line and apoptosis induction involved in it.