TY - JOUR
T1 - Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts
AU - Tsang, Chi Man
AU - Cheung, Yuk Chun
AU - Lui, Vivian Wai Yan
AU - Yip, Yim Ling
AU - Zhang, Guitao
AU - Lin, Victor Weitao
AU - Cheung, Kenneth Chat Pan
AU - Feng, Yibin
AU - Tsao, Sai Wah
N1 - Funding Information:
This project is funded by GRF grants awarded by the Hong Kong Research Grant Council (Grant number: 776608 M; 779810 M; 780911 M to SWT and 766211 to YB) and the RGC sponsored Area of Excellence Theme (Grant number: AoE/M-06/08 to MLL). VWL is supported by the Patricia L. Knebel Fund of the Pittsburgh Foundation, USA, the Career Development Program of the Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer (5P50 CA097190-05), the Head and Neck Cancer SPORE Developmental Research Award (5P50 CA097007). We thank PM Hau for his proficient advice and suggestions.
PY - 2013/12/31
Y1 - 2013/12/31
N2 - Background: Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented.Methods: In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models.Results: Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R.Conclusions: Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.
AB - Background: Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented.Methods: In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models.Results: Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R.Conclusions: Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.
UR - http://www.scopus.com/inward/record.url?scp=84891368877&partnerID=8YFLogxK
UR - https://publons.com/wos-op/publon/9815514/
U2 - 10.1186/1471-2407-13-619
DO - 10.1186/1471-2407-13-619
M3 - Journal article
C2 - 24380387
AN - SCOPUS:84891368877
SN - 1471-2407
VL - 13
JO - BMC Cancer
JF - BMC Cancer
M1 - 619
ER -