Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells

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• 作者：Thamizhiniyan Venkatesan ; Young-Woong Choi ; Sung-Phil Mun…
• 关键词：Anticancer source ; Autophagic inhibitor ; Breast cancer ; Lysosomal membrane permeabilization ; Pinus radiata ; Polyphenols
• 刊名：Cell Biology and Toxicology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：32
• 期：5
• 页码：451-464
• 全文大小：3,971 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Pharmacology and Toxicology
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-6822
• 卷排序：32

文摘

In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE-induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells.