FK-3000 isolated from Stephania delavayi Diels. inhibits MDA-MB-231 cell proliferation by decreasing NF-κB phosphorylation and COX-2 expression

Xu,Hong De; Cho,Soon-Chang; Bang,Mi-Ae; Bae,Chun-Sik; Choi,Yeonshik; Li,Yong-Chun; Lim,Seung-Kil; Shim,Jaegal; Park,Dae-Hun

doi:10.3892/ijo.2015.2940

FK-3000 isolated from Stephania delavayi Diels. inhibits MDA-MB-231 cell proliferation by decreasing NF-κB phosphorylation and COX-2 expression

Authors:
- Hong De Xu
- Soon-Chang Cho
- Mi-Ae Bang
- Chun-Sik Bae
- Yeonshik Choi
- Yong-Chun Li
- Seung-Kil Lim
- Jaegal Shim
- Dae-Hun Park
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Affiliations: School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, P.R. China, NaturePureKorea Inc., Jeonnam 517-8-3, Republic of Korea, Research Development Team, Jeonnam Biofood Technology Center, Jeonnam, Naju 520-330, Republic of Korea, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea, Department of Bio Medical Analysis, Korea Polytechnic College, Nonsan, Chungnam 320-905, Republic of Korea, Department of Exercise Prescription, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea, Comparative Biomedicine Research Branch, National Cancer Center, Goyang-si, Gyeonggi-do 411-769, Republic of Korea, Department of Oriental Medicine Materials, Dongshin University, Naju, Jeonnam 520-714, Republic of Korea
Published online on: March 27, 2015 https://doi.org/10.3892/ijo.2015.2940
Pages: 2309-2316
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The World Health Organization (WHO) has reported that cancer is one of the most prevalent diseases and a leading cause of death worldwide. Many anticancer drug development studies have been pursued over the last few decades and several viable drugs have been discovered, such as paclitaxel, topotecan and irinotecan. Previously, our research group uncovered the cytocidal and cytostatic effects of the plant Stephania delavayi Diels. In this study, we determined the active chemical to be 6,7-di-O-acetylsinococuline (FK-3000). The FK-3000 half maximal inhibitory concentration (IC50) in MDA-MB-231 breast carcinoma cells at 48 h was 0.52 µg/ml and it induced apoptosis in a dose- and time-dependent manner. FK-3000 suppressed NF-κB nuclear translocation, decreased NF-κB phosphorylation, and decreased COX-2 protein expression. MDA-MB-231 xenografted mice were treated with FK-3000, Taxol, or their combination for 21 days. The tumor size was smallest in the co-treatment group, indicating that FK-3000 may have a synergistic effect with Taxol. FK-3000 treatment showed no adverse effects on blood cell counts, serum protein levels, or pathology. These studies demonstrate that FK-3000, isolated from S. delavayi Diels., is a promising, pathway-specific anticancer agent that exhibits low toxicity.

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