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Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines

Gaillardin-induced apoptosis in breast cancer cell lines

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Abstract

Medicinal plant extracts have been widely used for cancer treatment. Gaillardin is a natural sesquiterpene lactone that has recently been reported to have anticancer properties. The ability to induce apoptosis is an important property of a candidate anticancer drug, which discriminates between anticancer drugs and toxic compounds. The current study was therefore carried out to address the issue if Gaillardin is able to induce apoptosis in the breast cancer cell lines MCF-7 and MDA-MB-468 and to determine the underlying mechanism of its anticancer effects. Apoptosis induction by Gaillardin treatment was confirmed by annexin V–FITC/PI staining, and caspase-3,-6, and-9 activation. Using Western blot analysis, we found that Gaillardin upregulated the pro-apoptotic protein Bax and p53 and downregulated the anti-apoptotic protein Bcl-2. Moreover, the apoptotic effect of Gaillardin was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). Taken together, these results demonstrate that Gaillardin can inhibit proliferation of breast cancer cells via inducing mitochondrial apoptotic pathway and therefore, might be a promising molecule in cancer chemoprevention or chemotherapy.

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Abbreviations

ΔΨm:

Mitochondrial membrane potential

MTT:

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

SLs:

Sesquiterpene lactones

ROS:

Reactive oxygen species

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Acknowledgments

The authors would like to thank the financial support of Cellular and Molecular Research Center of Qom University of Medical Sciences and also Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

    Faranak Fallahian & Mohammad Hossein Abdolmohammadi

  2. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Mahmoud Aghaei

  3. Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Hamzeloo-Moghadam

  4. Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Hamzeloo-Moghadam

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  1. Faranak Fallahian
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  2. Mahmoud Aghaei
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  3. Mohammad Hossein Abdolmohammadi
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  4. Maryam Hamzeloo-Moghadam
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Correspondence to Maryam Hamzeloo-Moghadam.

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Fallahian, F., Aghaei, M., Abdolmohammadi, M.H. et al. Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines. Cell Biol Toxicol 31, 295–305 (2015). https://doi.org/10.1007/s10565-016-9312-6

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