Abstract 2350: DATS prevented tumor progression and induced apoptotic death in an ectopic model of glioblastoma in SCID mice

Abstract

BACKGROUND: Glioblastoma, the most common and malignant brain tumor in humans, still remains incurable because of inefficacy of the currently available chemotherapeutic agents. Conventional chemotherapeutic agents have not been able to show promising results in glioblastoma patients for the last several decades. Therefore, new and non-conventional therapeutic agents also must be explored for controlling the growth of glioblastoma in vivo. Organosulfur compounds from garlic are well characterized and used as alternative medicine in many Asian countries. As a new treatment strategy in this investigation, we examined the anti-tumor properties of the most potent garlic compound diallyl trisulfide (DATS) in human glioblastoma U87MG xenografts in SCID mice. METHODS: We developed human glioblastoma U87MG xenografts in SCID mice for treatment with DATS for 7 days consecutively. The efficacy of DATS treatments in controlling tumor growth was assessed by histopathological examinations and also molecular analyses such as in situ immunofluorescent labeling and Western blotting. RESULTS: Our findings indicated that a range of DATS doses (10 μg/kg - 10 mg/kg) was effective in reducing tumor volume and weight in SCID mice ectopically xenografted with exponentially growing human glioblastoma U87MG cells. Histopathological examinations of the tumor sections showed significant amounts of inhibition of cell proliferation and induction of cell death. In addition, these findings were associated with a significant reduction in the number of mitotic bodies. Increase in TUNEL-positive staining was also detected in the tumor following treatment, suggesting that DATS induced apoptotic death in glioblastoma xenografts in SCID mice. Further, immunofluorescent staining of the tumor sections confirmed increase in expression of glial fibrillary acidic protein (GFAP), an acclaimed astrocyte-specific marker, in the tumors after the treatments. Our Western blotting demonstrated increases in the apoptosis promoting factors, reduction in the anti-apoptotic proteins (e.g., Bcl-2, BIRC proteins), and activation of the cysteine proteases such as calpain and caspase-3 to favor induction of apoptotic death in the tumors. It should also be mentioned that light microscopic examinations tissue sections revealed no damage in the livers and kidneys from the SCID mice following DATS treatments. CONCLUSIONS: Taken together, our results clearly demonstrated that DATS could be an effective therapeutic agent in preventing not only tumor progression but also induction of apoptosis in human glioblastoma in vivo. Success of our in vivo treatment of human glioblastoma xenografts with DATS strongly suggests that DATS should also be explored as a potential therapeutic agent for treatment glioblastoma in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2350. doi:1538-7445.AM2012-2350