Abstract
Our previous study indicated that anti-Fas antibody/actinomycin D (AF/AD) induced apoptosis of human hepatocellular carcinoma Bel-7402 cells; however, crosstalk influence between P38MAPK and autophagy on mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells remains unclear. Therefore, effect of AF/AD on apoptosis, autophagy, phosphorylated-P38MAPK (p-P38MAPK), and membrane potential (ΔΨm) with or without the P38MAPK inhibitor SB203580 or the autophagy inhibitor 3-methyladenine (3-MA) in Bel-7402 cells was investigated in the present study. The results showed that AF/AD resulted in induction of apoptosis concomitant with autophagy, upregulation of p-P38MAPK and autophagy-associated gene proteins (Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, and LC3 II), and downregulation of ΔΨm in Bel-7402 cells. In contrast, SB203580 attenuated the effects of AF/AD in Bel-7402 cells. Furthermore, the findings also demonstrated that 3-MA inhibited the impact of AF/AD on autophagy, Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, LC3 II, and ΔΨm, and promoted the influence of AF/AD on apoptosis and p-P38MAPK in Bel-7402 cells. Taken together, we conclude that crosstalk between P38MAPK and autophagy regulates mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells.
Highlights
Apoptosis (Type I programmed cell death) and autophagy (Type II programmed cell death) are discrete cellular processes that play a crucial role during development and maintenance of tissue homeostasis
The results indicate that crosstalk between P38MAPK and autophagy might regulate mitochondria-mediated apoptosis induced by antibody/actinomycin D (AF/actinomycin D (AD)) in Bel-7402 cells
Apoptosis with autophagy in Bel-7402 and cells, the the occurrence of apoptosis and induced autophagy was concomitant detected by inverted microscope electron occurrence of apoptosis and autophagy was detected by inverted microscope and electron microcopy microcopy assay
Summary
Apoptosis (Type I programmed cell death) and autophagy (Type II programmed cell death) are discrete cellular processes that play a crucial role during development and maintenance of tissue homeostasis. Recent studies have suggested that apoptosis and autophagy are two key pathways in treatment process of anticancer drugs [1,2]. Accumulating evidence has demonstrated that mitochondrial membrane permeabilization is a key event in drugs-induced apoptosis and autophagy of cancer cells [3,4,5]. P38 mitogen-activated protein kinase (MAPK), a member of the MAPK family, plays a key regulatory role in cell proliferation, apoptosis, and autophagy. Past reports have shown that P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by drugs in cancer cells [6,7]
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