The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling

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The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling. / Lange, Nicole; Tontsa, Armelle Tsamo; Wegscheid, Claudia; Mkounga, Pierre; Nkengfack, Augustin Ephrem; Loscher, Christine; Sass, Gabriele; Tiegs, Gisa.

In: PLOS ONE, Vol. 11, No. 8, 2016, p. e0160843.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Lange, N, Tontsa, AT, Wegscheid, C, Mkounga, P, Nkengfack, AE, Loscher, C, Sass, G & Tiegs, G 2016, 'The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling', PLOS ONE, vol. 11, no. 8, pp. e0160843. https://doi.org/10.1371/journal.pone.0160843

APA

Lange, N., Tontsa, A. T., Wegscheid, C., Mkounga, P., Nkengfack, A. E., Loscher, C., Sass, G., & Tiegs, G. (2016). The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling. PLOS ONE, 11(8), e0160843. https://doi.org/10.1371/journal.pone.0160843

Vancouver

Bibtex

@article{fe9521ff309f43fdaae2a0596c8db940,
title = "The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling",
abstract = "Hepatocellular carcinoma (HCC) is extremely resistant towards pharmacological therapy. To date, the multi-kinase inhibitor Sorafenib is the only available therapeutic agent with the potential to prolong patient survival. Using the human hepatoma cell lines HepG2 and Huh7, we analyzed anti-cancer activities of 6 purified havanensin type limonoids isolated from the traditional African medicinal plant Trichilia rubescens Oliv. Our results show that two of the compounds, TR4 (TS3) and TR9 (Rubescin E) reduced hepatoma cell viability, but not primary hepatocyte viability, at TC50s of 5 to 10 μM. These were significantly lower than the TC50s for Sorafenib, the histone deacetylase inhibitor SAHA or 5-Fluoruracil. In comparison, TR3 (Rubescin D), a limonoid isolated in parallel and structurally highly similar to TR4 and TR9, did not interfere with hepatoma cell viability. Both, TR4 and TR9, but not TR3, induced apoptosis in hepatoma cells and interfered with NF-κB activation. TR4 as well as TR9 significantly supported anti-cancer activities of Sorafenib. In summary, the limonoids TR4 and TR9 exhibit anti-cancer activities and support Sorafenib effects in vitro, having the potential to support future HCC therapy.",
keywords = "Journal Article",
author = "Nicole Lange and Tontsa, {Armelle Tsamo} and Claudia Wegscheid and Pierre Mkounga and Nkengfack, {Augustin Ephrem} and Christine Loscher and Gabriele Sass and Gisa Tiegs",
year = "2016",
doi = "10.1371/journal.pone.0160843",
language = "English",
volume = "11",
pages = "e0160843",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - The Limonoids TS3 and Rubescin E Induce Apoptosis in Human Hepatoma Cell Lines and Interfere with NF-κB Signaling

AU - Lange, Nicole

AU - Tontsa, Armelle Tsamo

AU - Wegscheid, Claudia

AU - Mkounga, Pierre

AU - Nkengfack, Augustin Ephrem

AU - Loscher, Christine

AU - Sass, Gabriele

AU - Tiegs, Gisa

PY - 2016

Y1 - 2016

N2 - Hepatocellular carcinoma (HCC) is extremely resistant towards pharmacological therapy. To date, the multi-kinase inhibitor Sorafenib is the only available therapeutic agent with the potential to prolong patient survival. Using the human hepatoma cell lines HepG2 and Huh7, we analyzed anti-cancer activities of 6 purified havanensin type limonoids isolated from the traditional African medicinal plant Trichilia rubescens Oliv. Our results show that two of the compounds, TR4 (TS3) and TR9 (Rubescin E) reduced hepatoma cell viability, but not primary hepatocyte viability, at TC50s of 5 to 10 μM. These were significantly lower than the TC50s for Sorafenib, the histone deacetylase inhibitor SAHA or 5-Fluoruracil. In comparison, TR3 (Rubescin D), a limonoid isolated in parallel and structurally highly similar to TR4 and TR9, did not interfere with hepatoma cell viability. Both, TR4 and TR9, but not TR3, induced apoptosis in hepatoma cells and interfered with NF-κB activation. TR4 as well as TR9 significantly supported anti-cancer activities of Sorafenib. In summary, the limonoids TR4 and TR9 exhibit anti-cancer activities and support Sorafenib effects in vitro, having the potential to support future HCC therapy.

AB - Hepatocellular carcinoma (HCC) is extremely resistant towards pharmacological therapy. To date, the multi-kinase inhibitor Sorafenib is the only available therapeutic agent with the potential to prolong patient survival. Using the human hepatoma cell lines HepG2 and Huh7, we analyzed anti-cancer activities of 6 purified havanensin type limonoids isolated from the traditional African medicinal plant Trichilia rubescens Oliv. Our results show that two of the compounds, TR4 (TS3) and TR9 (Rubescin E) reduced hepatoma cell viability, but not primary hepatocyte viability, at TC50s of 5 to 10 μM. These were significantly lower than the TC50s for Sorafenib, the histone deacetylase inhibitor SAHA or 5-Fluoruracil. In comparison, TR3 (Rubescin D), a limonoid isolated in parallel and structurally highly similar to TR4 and TR9, did not interfere with hepatoma cell viability. Both, TR4 and TR9, but not TR3, induced apoptosis in hepatoma cells and interfered with NF-κB activation. TR4 as well as TR9 significantly supported anti-cancer activities of Sorafenib. In summary, the limonoids TR4 and TR9 exhibit anti-cancer activities and support Sorafenib effects in vitro, having the potential to support future HCC therapy.

KW - Journal Article

U2 - 10.1371/journal.pone.0160843

DO - 10.1371/journal.pone.0160843

M3 - SCORING: Journal article

C2 - 27518192

VL - 11

SP - e0160843

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 8

ER -