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Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells

  • Kyung Hun Kim
  • Hye Sook Seo
  • Han Seok Choi
  • InHwa Choi
  • Yong Cheol Shin
  • Seong-Gyu KoEmail author
Research Articles Drug Actions

Abstract

Ursolic acid (3-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid derived from leaves, berries, fruits, and flowers of medicinal plants, such as Rosemarinus officinalis. Ursolic acid has been shown to inhibit tumorigenesis, tumor promotion, and suppress angiogenesis. In our present study, we found that ursolic acid decreased cell proliferation rate and induce apoptosis in human breast cancer cell line, MDA-MB-231. When we checked the expression levels of proteins associated with apoptosis signal by using immunoblotting, we found that ursolic acid induces various apoptotic molecules related to either extrinsic or intrinsic apoptosis signal pathway in MDA-MB-231 cells. In our study, we found that ursolic acid induced the appearance of Fas receptor and cleavage of caspase-8, -3 and PARP. We also found that ursolic acid induced Bax up-regulation and Bcl-2 down-regulation and release of cytochrome C to the cytosol from mitochondria. Moreover, ursolic acid cleaved caspase-9 and decreased mitochondrial membrane potential (ΔΨm) as shown with JC-1 staining. These data indicate that ursolic acid induce apoptosis through both mitochondrial death pathway and extrinsic death receptor dependent pathway in MDA-MB-231 cells. Our data clearly indicate that ursolic acid could be used as a potential anticancer drug for breast cancer.

Key words

Ursolic acid Fas caspases Bcl-2 Bax 

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Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2011

Authors and Affiliations

  • Kyung Hun Kim
    • 1
  • Hye Sook Seo
    • 1
  • Han Seok Choi
    • 1
  • InHwa Choi
    • 2
  • Yong Cheol Shin
    • 1
  • Seong-Gyu Ko
    • 1
  1. 1.Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and GenomicsKyung Hee UniversitySeoulKorea
  2. 2.Department of Oriental Ophthalmology, Otorhinolaryngology and Dermatology, Institute of Oriental Medicine and College of Oriental MedicineKyung Hee UniversitySeoulKorea

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