Abstract B49: Oral administration of ethanol extract of Descurainia sophia (KIOM-CRC#5) attenuates A549 xenograft lung cancer growth in murine orthotopic lung cancer model through blocking Stat3 signaling

Abstract

Abstract Lung cancer is the most frequent malignancy and also one of the leading causes of mortality in both men and women worldwide. Despite current advances in diagnostics and medicines, the incidence of lung cancer is increasing and effective treatment is very challenging. These facts emphasize on the importance of both proper animal models and seeking anticancer materials from traditionally used herbal materials for developing therapy for lung cancer. Here we developed a murine orthotopic lung cancer model using A549 human lung cancer cell line orthotopically injected to the lung of immune-impaired Balb/c mice for measuring the anticancer effect of Traditional Korean medicinal herb, Descurainia sophia. Traditional use of D.Sophia includes relieving cough, chest pain, and many other symptoms which commonly accompanied with lung cancer. Our data showed oral administration of KIOM-CRC#5, an ethanol extract of Descurainia sophia, effectively attenuated the lung tumor growth in this animal model after 4 weeks of drug administration. This effect was even greater in the pretreatment group, which received 5 times/week KIOM-CRC#5 administration for 3 weeks prior to tumor cell injection. In vitro study revealed that Stat3 phosphorylation at Tyr 705 site was rapidly diminished in A549 cells treated with KIOM-CRC#5 as low as 5μg/ml and the expressions of downstream targets of Stat3 including c-Myc and cyclin D1 were also abolished. Additionally, Stat3 reporter assay showed marked reduction of transcriptional activity of Stat3 in KIOM-CRC#5 treated cells. In the present study, we developed a murine model of orthotopic lung tumor, which can be useful in the screening and testing the efficacy of therapeutic candidates from medicinal herbs, and tested the anticancer activity of ethanol extract of Descurainia Sophia (KIOM-CRC#5). Oral admistration of KIOM-CRC#5 attenuated orthotopic lung tumor growth possible through blocking the Stat3 signaling pathway, which is hyper-activated in many cancers including lung cancer. Considering that there was no adverse effect related with the oral administration of KIOM-CRC#5 in the tested animals and its effect on blocking tumor growth in vivo as well as potent cytotoxic effect on various cancer cell lines in vitro, KIOM-CRC#5 can be a good candidate for chemotherapeutic agent for lung cancer. Citation Format: Jinhee Kim, Jong-Shik Park, Myung-Gi Baek, Haejin Kim, You Jin Lee, Jun Lee, No Soo Kim, Ok-Sun Bang. Oral administration of ethanol extract of Descurainia sophia (KIOM-CRC#5) attenuates A549 xenograft lung cancer growth in murine orthotopic lung cancer model through blocking Stat3 signaling. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B49.