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Resistance to chemoprevention:

When tumor cells refuse to stop

Munich, 05/26/2011

In the context of cancer therapy, natural products find application primarily as chemopreventive agents. These are intended to stop premalignant cells from developing into full-blown tumors and giving rise to metastases. A team led by chemist Priv.-Doz. Dr Beatrice Bachmeier LMU Munich University Hospital and Professor Thomas Efferth of Johannes Gutenberg University in Mainz have now uncovered a mechanism that enables tumor cells to evade the inhibitory effect of one such compound, causing the treatment to fail. The researchers studied breast cancer cells which no longer responded to artesunate. Artesunate, which is also used to treat malaria, is closely related to the artemisins, a group of chemicals synthesized by plants of the genus Artemisia (mugworts). Because artemisins induce practically no side-effects, they are suitable for long-term use, either to protect individuals who are particularly at risk of developing cancer or to check the growth of an established cancer. As Bachmeier, Efferth and their coworkers have now shown, many tumor cells make use of the transcription factor NF-κB to develop resistance to the action of artesunate. NF-κB is less active in normal cells than in cancer cells – and so is a potential drug target for cancer therapy. Activation of NF-κB blocks the initiation of programmed cell death (apoptosis) – the process that drives damaged or diseased cells to commit suicide. Hence the activated transcription factor makes tumor cells unresponsive to the restraints that normally control cell proliferation. “We have identified the factor responsible for resistance to artesunate,” says Bachmeier. “We hope that this finding will help us to regain control over the transcription factor, so that the chemopreventive effect can be restored.” (suwe/PH)


“Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells”
Beatrice Bachmeier, Iduna Fichtner, Peter H. Killian, Emanuel Kronski, Ulrich Pfeffer, Thomas Efferth
PloS One; 26 May 2011


Priv.-Doz. Dr Beatrice Bachmeier
Division of Clinical Chemistry and Clinical Biochemistry at the LMU Munich university hospital
Phone: +49 (0) 89 / 5160-2650
Mobil: +49 (0) 170 / 283 97 40

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