Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells

被引：84

作者：

Han, Songhee ^{[1
]}

Jeong, Ae Jin ^{[1
,2
]}

Yang, Heejung ^{[3
]}

Bin Kang, Kyo ^{[4
,5
]}

Lee, Haeri ^{[1
,2
]}

Yi, Eun Hee ^{[1
,6
]}

Kim, Byung-Hak ^{[1
,7
]}

Cho, Chung-Hyun ^{[1
,6
,8
]}

Chung, Jin Woong ^{[9
]}

Sung, Sang Hyun ^{[4
,5
]}

Ye, Sang-Kyu ^{[1
,6
,7
,10
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Pharmacol & Biomed Sci, 103 Daehangno, Seoul 03080, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea

[3] Kangwon Natl Univ, Coll Pharm, Chunchon 24341, South Korea

[4] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea

[5] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 08826, South Korea

[6] Seoul Natl Univ, Coll Med, Ischem Hypox Dis Inst, Seoul 03080, South Korea

[7] Seoul Natl Univ, Coll Med, Biomed Sci Project BK2IPLUS, Seoul 03080, South Korea

[8] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea

[9] Dong A Univ, Dept Biol Sci, Busan 47315, South Korea

[10] Seoul Natl Univ, Coll Med, Neuroimmune Informat Storage Network Res Ctr, Seoul 03080, South Korea

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2016年 / 194卷

基金：

新加坡国家研究基金会;

关键词：

Colorectal cancer (CRC); Interleukin-6 (IL-6); Ginsenoside 20(S)-Rh2; Matrix metalloproteinase (MMP); Signal transducer and activator of transcription 3 (STAT3); STAT3; ACTIVATION; COLON-CANCER; IN-VITRO; SIGNALING PATHWAY; LIVER METASTASES; RED GINSENG; DOXORUBICIN; INFLAMMATION; INHIBITOR; SURVIVAL;

D O I：

10.1016/j.jep.2016.08.039

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Ethnopharmacological relevance: Panax ginseng is one of the most well-known medicinal herbs in Korea and China, which has been used for treatment and prevention of cancer, obesity, diabetes, and cardiovascular diseases. Ginsenosides are the major components of P. ginseng, having a wide range of pharmacological activities. Among the ginsenosides, protopanaxadiol (PPD)-types reportedly have potent anti-cancer effects. Rh2 is PPD-type ginsenoside, and two stereoisomeric forms of Rh2 as 20(S)- and 20 (R)-Rh2 were selectively isolated recently. Aim of the study: The biological activities of Rh2 ginsenosides are known to depend on their differences in stereochemistry. Colorectal cancer (CRC) is one of the most lethal neoplasm, and cancer-related death is usually associated with metastasis to other organs. We aimed this study to investigate whether 20(S)- and 20(R)-Rh2 can suppress tumor invasion in human CRC cells. Materials and methods: 20(S)- and 20(R)-Rh2 were isolated from the roots of ginseng. Human CRC cells were incubated with 20(S)- or 20(R)-Rh2 in the presence or absence of interleukin-6. An MIT assay was used to measure cell viability. Western blot and quantitative real-time PCR analyses were performed to determine levels of expression and phosphorylation. An invasion assay was performed using a Boyden chamber system with the Matrigel-coated membrane to measure cancer cell invasion. Results: 20(S)- and 20(R)-Rh2 showed differential cytotoxic activity. Only 20(S)-Rh2 decreased cancer cell viability. Additionally, 20(S)-Rh2 effectively inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of matrix metalloproteinases (MMPs), including MMP-1, 2, and 9, resulting in inhibition of cancer cell invasion. Interestingly, these pharmacological activities of 20(S)-Rh2 were more potent than those of 20(R)-Rh2. Furthermore, combination treatment showed that 20(S)-Rh2 enhanced the sensitization of doxorubicin-treated anti-cancer activities in CRC cells. Conclusion: Our results demonstrated that ginsenoside 20(S)-Rh2 has therapeutic potential for the treatment with CRC and may be valuable as a combination partner with more classic chemotherapeutic agents, such as doxorubicin, to treat CRC. (C) 2016 Published by Elsevier Ireland Ltd.

引用

页码：83 / 90

页数：8