Waltonitone induces human hepatocellular carcinoma cells apoptosis in vitro and in vivo

Zhang, Zhang; Wang, Shuo; Qiu, Hong; Duan, Chaohui; Ding, Kan; Wang, Zhengtao

doi:10.1016/j.canlet.2009.05.023

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Volume 286, Issue 2 , Pages 223-231, 28 December 2009

Waltonitone induces human hepatocellular carcinoma cells apoptosis in vitro and in vivo

Zhang Zhang
- Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Cai Lun Road 1200, Shanghai 201203, China
- Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zu Chong Zhi Road 555, Shanghai 201203, China
Shuo Wang
- Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zu Chong Zhi Road 555, Shanghai 201203, China
Hong Qiu
- Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zu Chong Zhi Road 555, Shanghai 201203, China
Chaohui Duan
- Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Cai Lun Road 1200, Shanghai 201203, China
Kan Ding
- Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zu Chong Zhi Road 555, Shanghai 201203, China
- Corresponding authors. Tel./fax: +86 21 50806928 (K. Ding), tel.: +86 21 51322507; fax: +86 21 51322519 (Z.-T. Wang).
Zhengtao Wang
- Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Cai Lun Road 1200, Shanghai 201203, China
- Corresponding authors. Tel./fax: +86 21 50806928 (K. Ding), tel.: +86 21 51322507; fax: +86 21 51322519 (Z.-T. Wang).

Received 27 March 2009; received in revised form 25 May 2009; accepted 26 May 2009. published online 18 June 2009.

Abstract

Waltonitone, a new ursane-type pentacyclic triterpene isolated from Gentian waltonii Burkill significantly inhibited human hepatocellular carcinoma BEL-7402 cells growth. Apoptosis induced by waltonitone was characterized by AO/EB staining and flow cytometric analysis. Apoptosis microarray assay results showed BCL-2 family genes might especially play an important role in waltonitone-induced apoptosis. RT-PCR and Western blotting analysis showed that waltonitone could induce tumor cell apoptosis via both death receptor and mitochondria pathways. Meanwhile, the inhibitory effect of waltonitone was examined in vivo using BEL-7402 tumor cells xenografted into athymic mice model. In summary, these studies demonstrated that waltonitone might inhibit hepatocellular carcinoma cells growth and induce apoptosis in vitro and in vivo.

Keywords: Gentiana waltonii Burkill, Waltonitone, Hepatocellular carcinoma, Apoptosis, Caspase