Artocarpus communis induces autophagic instead of apoptotic cell death in human hepatocellular carcinoma cells

Cheng Wei Tzeng, Wen Sheng Tzeng, Liang Tzung Lin, Chiang Wen Lee, Ming Hong Yen, Feng Lin Yen, Chun Ching Lin

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9 Citations (Scopus)

Abstract

For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.

Original languageEnglish
Pages (from-to)559-579
Number of pages21
JournalAmerican Journal of Chinese Medicine
Volume43
Issue number3
DOIs
Publication statusPublished - May 14 2015

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Keywords

  • Antihepatoma Activity
  • Apoptosis
  • Artocarpus communis
  • Autophagy
  • Chemotherapy Agent
  • Hepatocellular Carcinoma

ASJC Scopus subject areas

  • Complementary and alternative medicine

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