Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Apoptosis and Autophagy Induction of A549 Human Lung Cancer Cells by Methylene Chloride Extracts of Morus alba L.

A549 인체폐암세포에서 상백피 메틸렌클로라이드 추출물에 의한 Apoptosis 및 Autophagy 유발

  • Park, Shin-Hyoung (Departments of Pathology, College of Oriental Medicine, Dongeui University) ;
  • Chi, Gyoo-Yong (Departments of Pathology, College of Oriental Medicine, Dongeui University) ;
  • Choi, Yung-Hyun (Biochemistry, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University) ;
  • Eom, Hyun-Sup (Departments of Pathology, College of Oriental Medicine, Dongeui University)
  • 박신형 (동의대학교 한의과대학 병리학교실) ;
  • 지규용 (동의대학교 한의과대학 병리학교실) ;
  • 최영현 (동의대학교 생화학교실 및 한의학연구소) ;
  • 엄현섭 (동의대학교 한의과대학 병리학교실)
  • Received : 2010.10.28
  • Accepted : 2010.11.30
  • Published : 2010.12.25
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Abstract

Morus alba L., a kind of Oriental medicinal herbs, has been traditionally used to treat pulmonary asthma and congestion. According to recent studies, extracts of M. alba L. have showed anti-inflammatory, anti-oxidant, anti-tumor and hypoglycemic effects. However, the molecular mechanisms on how it acts as a death-inducer in cancer cells have not been fully understood. In this study, we investigated the cell death effects of methylene chloride extracts of M. alba L. (MEMA) in A549 human lung carcinoma cells. It was shown that MEMA induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. MEMA treatment induced the expression of death receptor-related proteins such as death receptor (DR) 4, DR5, Fas and FasL, which further triggered the activation of caspase-8 and the cleavage of Bid in a concentration-dependent manner. However, MEMA reduced anti-apoptotic Bcl-2 and Bcl-xL expression which contributed to the loss of mitochondrial membrane potential (MMP), and the activations of caspase-9 and caspase-3. Meanwhile, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in MEMA-treated cells. Furthermore, markers of autophagy, namely, the increased MDC-positive cells, conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Taken together, these findings demonstrated that MEMA triggered both autophagy and apoptosis in A549 cancer cells. They might suggest that M. alba L. could be a prospective clinical application to treat human lung cancers.

Keywords

References

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