α-Mangostin: A Dietary Antioxidant Derived from the Pericarp of Garcinia mangostana L. Inhibits Pancreatic Tumor Growth in Xenograft Mouse Model

被引：33
作者：
Bin Hafeez, Bilal [1 ]
Mustafa, Ala [1 ]
Fischer, Joseph W. [1 ]
Singh, Ashok [1 ]
Zhong, Weixiong [2 ]
Shekhani, Mohammed Ozair [1 ]
Meske, Louise [1 ]
Havighurst, Thomas [3 ]
Kim, KyungMann [3 ]
Verma, Ajit Kumar [1 ]
机构：
[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Human Oncol, Wisconsin Inst Med Res,Paul Carbone Comprehens Ca, Madison, WI 53792 USA
[2] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Inst Med Res, Dept Pathol, Madison, WI 53792 USA
[3] Univ Wisconsin, Sch Med & Publ Hlth, Paul Carbone Comprehens Canc Ctr, Dept Biostat & Med Informat, Madison, WI 53792 USA
来源：
ANTIOXIDANTS & REDOX SIGNALING | 2014年 / 21卷 / 05期
关键词：
NF-KAPPA-B; CANCER-CELLS; SIGNALING PATHWAY; IN-VIVO; INDUCED APOPTOSIS; DOWN-REGULATION; MAMMARY-CANCER; STAT3; GEMCITABINE; METASTASIS;
D O I：
10.1089/ars.2013.5212
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of alpha-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. Results: The chemotherapeutic effect of alpha-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). alpha-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. alpha-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, alpha-mangostin inhibited the expression levels of pNF-kappa B/p65Ser552, pStat3Ser727, and pStat3Tyr705. alpha-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-kappa B) and signal transducer and activator 3 (Stat3). alpha-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of alpha-mangostin (6 mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with alpha-mangostin. alpha-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. Innovation: We present, for the first time, that dietary antioxidant alpha-mangostin inhibits the growth of PC cells in vitro and in vivo. Conclusion: These results suggest the potential therapeutic efficacy of alpha-mangostin against human PC.
引用
收藏
页码：682 / 699
页数：18
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