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Apoptosis of HeLa cells induced by a new targeting photosensitizer-based PDT via a mitochondrial pathway and ER stress

Authors Li D, Li L, Li P, Li Y, Chen X

Received 24 October 2014

Accepted for publication 31 December 2014

Published 7 April 2015 Volume 2015:8 Pages 703—711


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati

Donghong Li,1 Lei Li,2 Pengxi Li,1 Yi Li,3 Xiangyun Chen1

1State Key Laboratory of Trauma, Burn and Combined Injury, The Second Department of Research Institute of Surgery, 2The First Department of Research Institute of Surgery, 3Cancer Center, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China

Abstract: Photodynamic therapy (PDT) is emerging as a viable treatment for many cancers. To decrease the cutaneous photosensitivity induced by PDT, many attempts have been made to search for a targeting photosensitizer; however, few reports describe the molecular mechanism of PDT mediated by this type of targeting photosensitizer. The present study aimed to investigate the molecular mechanism of PDT induced by a new targeting photosensitizer (PS I), reported previously by us, on HeLa cells. Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells. PS I PDT resulted in rapid increases in intracellular reactive oxygen species (ROS) production and Ca2+ concentration, both of which reached a peak nearly simultaneously at 15 minutes, followed by the loss of mitochondrial membrane potential at 30 minutes, release of cytochrome c from mitochondria into the cytoplasm, downregulation of Bcl-2 expression, and upregulation of Bax expression. Meanwhile, activation of caspase-3, -9, and -12, as well as induction of C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP78), in HeLa cells after PS I PDT was also detected. These results suggest that apoptosis of HeLa cells induced by PS I PDT is not only triggered by ROS but is also regulated by Ca2+ overload. Mitochondria and the ER serve as the subcellular targets of PS I PDT, the effective activation of which is responsible for PS I PDT-induced apoptosis in HeLa cells.

Keywords: folate-PEG-chlorin, folate receptor positive cells, cell death model, mechanism

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