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

Han, Songhee; Jeong, Ae Jin; Yang, Heejung; Kang, Kyo Bin; Lee, Haeri; Yi, Eun Hee; Kim, Byung Hak; Cho, Chung Hyun; Chung, Jin Woong; Sung, Sang Hyun; Ye, Sang Kyu

doi:10.1016/j.jep.2016.08.039

Cited by 80 publications

(37 citation statements)

References 46 publications

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“…As shown in the example above, when an enantiomer of a useful substance exists under development, it should be verified that there is a difference in activity depending on each form. Although studies on the anti-cancer activity of ginsenoside Rh2 have been performed on lung, breast, liver, colorectal cancers, and leukemia, there has been no study of the cellular pattern of cancer cells when Rh2 was treated in real-time (Ge, Yan, & Cai, 2017;Han et al, 2016;Kim & Choi, 2016;Li, Li, Dong, Wang, & Li, 2017;Ren, Shi, Teng, & Yao, 2018;Wan et al, 2017). Among the existing studies, there is a study on how Rh2 using HCT-116 cells can act as a specific mechanism of anti-cancer activity for a colorectal cell line (Han et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

A stereo-selective growth inhibition profile of ginsenoside Rh2 on human colon cancer cells

Jeong

Ku²,

You

et al. 2019

CyTA - Journal of Food

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We compared the stereo-selective growth inhibition effects of purified enantiomeric pairs of ginsenoside Rh2 (20(S)-ginsenoside Rh2 and 20(R)-ginsenoside Rh2) on human colon cancer cells in vitro with non-invasive real-time cellular analysis. When 50 μM, respectively, of 20(S)-ginsenoside Rh2 and 20(R)-ginsenoside Rh2 were administered to the colon cancer cell line HT-29, only the S-type ginsenoside Rh2 lowered cancer cell viability. Similarly, when the same experiment was conducted on cancer cells with different levels of ginsenoside treatments (20, 40, 60, and 80 μM), cancer cell viability was decreased in a dose-dependent manner only in the 20(S)-ginsenoside Rh2 treatment groups. Cytotoxicity of cancer cells was observed only in the S form-treated group when cellular response and growth pattern were analyzed via real-time cellular analysis. These findings suggest that the anti-tumor effect of ginsenoside Rh2 on colon cancer cells is S-form selective. Perfil de inhibición del crecimiento estereoselectivo de ginsenósido Rh2 en células de cáncer de colon humano RESUMEN En el presente estudio se compararon los efectos de inhibición del crecimiento estereoselectivo de pares enantioméricos purificados de ginsenósido Rh2 (20 (S)-ginsenósido Rh2 y 20 (R)-ginsenósido Rh2) en células de cáncer de colon humano in vitro, empleando para ello un análisis celular no invasivo en tiempo real. Cuando se administraron 50 μM de 20 (S)-ginsenósido Rh2 y de 20 (R)-ginsenósido Rh2 a la línea celular de cáncer de colon HT-29, se constató que solo el ginsenósido Rh2 de tipo S disminuyó la viabilidad de las células cancerosas. De manera similar, al realizar el mismo experimento en células cancerosas expuestas a diferentes niveles de tratamientos con ginsenósidos (20, 40, 60 y 80 µM), se comprobó que la viabilidad de las células cancerosas se redujo de manera dependiente de la dosis solo en los grupos tratados con 20 (S)-ginsenósido Rh2. Asimismo, cuando se examinó la respuesta celular y el patrón de crecimiento a través de análisis celular en tiempo real se observó que las células cancerosas mostraron citotoxicidad solo en el grupo tratado con la forma S. Estos hallazgos sugieren que el efecto antitumoral del ginsenósido Rh2 en células de cáncer de colon es selectivo en su forma S.

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Section: Discussionmentioning

confidence: 99%

A stereo-selective growth inhibition profile of ginsenoside Rh2 on human colon cancer cells

Jeong

Ku²,

You

et al. 2019

CyTA - Journal of Food

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“…In the inhibitory pathway, Rh2 inhibited the lipopolysaccharide-induced production of nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 [6] . Rh2 has been shown to have anticancer activity in a variety of cancer cells without having any remarkable toxicity [7] , including in lung [8] , liver [9] , breast [10] , prostate [11] , and colorectal [12] cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells

Lee

Jeong

et al. 2018

Journal of Ginseng Research

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BackgroundGinsenoside Rh2 has been known to enhance the activity of immune cells, as well as to inhibit the growth of tumor cells. Although the repertoire of genes regulated by Rh2 is well-known in many cancer cells, the epigenetic regulation has yet to be determined, especially for comprehensive approaches to detect methylation changes.MethodsThe effect of Rh2 on genome-wide DNA methylation changes in breast cancer cells was examined by treating cultured MCF-7 with Rh2. Pyrosequencing analysis was carried out to measure the methylation level of a global methylation marker, LINE1. Genome-wide methylation analysis was carried out to identify epigenetically regulated genes and to elucidate the most prominent signaling pathway affected by Rh2. Apoptosis and proliferation were monitored to examine the cellular effect of Rh2.ResultsLINE1 showed induction of hypomethylation at specific CpGs by 1.6–9.1% (p < 0.05). Genome-wide methylation analysis identified the “cell-mediated immune response”-related pathway as the top network. Cell proliferation of MCF-7 was retarded by Rh2 in a dose-dependent manner. Hypermethylated genes such as CASP1, INSL5, and OR52A1 showed downregulation in the Rh2-treated MCF-7, while hypomethylated genes such as CLINT1, ST3GAL4, and C1orf198 showed upregulation. Notably, a higher survival rate was associated with lower expression of INSL5 and OR52A1 in breast cancer patients, while with higher expression of CLINT1.ConclusionThe results indicate that Rh2 induces epigenetic methylation changes in genes involved in immune response and tumorigenesis, thereby contributing to enhanced immunogenicity and inhibiting the growth of cancer cells.

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“…The specific effects of Rh2 include apoptosis promotion as well as inhibition of significant growth, metastasis, and invasion (4,(6)(7)(8). Although some signaling pathways such as epidermal growth factor receptor (9), tumor necrosis factor-α (10), Janus kinase/signal transducer and activator of transcription 3 (11), and phosphoinositide 3-kinase/Akt (7) have been implicated in the regulatory process of Rh2 in cancer cells, the detailed mechanism remains unclear, particularly the role of non-coding RNAs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑146a‑5p enhances ginsenoside Rh2‑induced anti‑proliferation and the apoptosis of the human liver cancer cell line HepG2

Chen

Chu

et al. 2018

Oncol Lett

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Liver cancer is one of the leading causes of malignancy-associated mortality worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2 (Rh2) has been reported to have antitumor effects on some types of cancer, including liver cancer. However, its regulatory mechanism has not been extensively evaluated. In the present study, Rh2 increased the expression of microRNA (miR)-200b-5p, miR-224-3p and miR-146a-5p, and decreased the expression of miR-26b-3p and miR-29a-5p. Of the three upregulated miRs, miR-146a-5p exhibited the highest fold elevation. In accordance with a previous study, Rh2 effectively inhibited the survival of liver cancer cells and in a mouse model. In addition, it was observed that Rh2 markedly promoted liver cancer apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of cell survival as well as colony formation induced by Rh2 were enhanced and weakened by miR-146a-5p overexpression and inhibition, respectively. The results of the present study provide further evidence of the antitumor effect of Rh2 in liver cancer and also demonstrate that this effect may be mediated via the regulation of miR-146a-5p expression in the liver cancer cell line HepG2. The results indicated that miR-146a-5p may be a promising regulatory factor in Rh2-mediated effects in liver cancer.

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

Cited by 80 publications

References 46 publications

A stereo-selective growth inhibition profile of ginsenoside Rh2 on human colon cancer cells

A stereo-selective growth inhibition profile of ginsenoside Rh2 on human colon cancer cells

Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells

MicroRNA‑146a‑5p enhances ginsenoside Rh2‑induced anti‑proliferation and the apoptosis of the human liver cancer cell line HepG2

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