scholarly journals Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma

Oncotarget ◽  
2014 ◽  
Vol 5 (13) ◽  
pp. 4845-4854 ◽  
Author(s):  
Yu-Jen Chen ◽  
Chih-Wen Chi ◽  
Wen-Chi Su ◽  
Huey-Lan Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Human Hepatocellular Carcinoma ◽  
Autophagic Cell Death

Artocarpus communis Induces Autophagic Instead of Apoptotic Cell Death in Human Hepatocellular Carcinoma Cells

2015 ◽  
Vol 43 (03) ◽  
pp. 559-579 ◽  
Author(s):  
Cheng-Wei Tzeng ◽  
Wen-Sheng Tzeng ◽  
Liang-Tzung Lin ◽  
Chiang-Wen Lee ◽  
Ming-Hong Yen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Hepatoma Cell ◽  
Apoptotic Cell Death ◽  
Human Hepatocellular Carcinoma ◽  
Acridine Orange Staining ◽  
Hepatoma Cell Lines

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.

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