期刊
EUROPEAN JOURNAL OF CANCER
卷 48, 期 13, 页码 2086-2096出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2011.10.013
关键词
Photosensitiser; PHOTOCYANINE; ROS; Mitochondrial membrane; Hepatocellular carcinoma; Apoptosis; Cell cycle
类别
资金
- Creation Platform Project of Fujian Provincial Science and Technology Bureau [2009Y2004]
- Young Scientist Innovation Foundation of Fujian Province of China [2007F0347]
- Scientific and Technological Foundation of Fujian Province of China [JA08004, 2008J0001, JA09016, JA09011]
- Scientific and Technological Foundation of Fuzhou University [826804]
Photodynamic therapy (PDT) has been accepted as an alternative treatment for cancer. The rationale for the development of PDT for cancer is that target specificity can be achieved by controlling the location at which light activates the drug, i.e. photosensitiser. Metal phthalocyanines represent a new class of photosensitisers developed for cancer treatment. In the present study, we focused on exploring molecular mechanisms of the lead photosensitiser PHOTOCYANINE on hepatocellular carcinoma (HCC) HepG2 cells to guide our future development of PHOTOCYANINE. Growth inhibition potency of PHOTOCYANINE and its analogues was tested in vitro with and without irradiation at wavelength 670 nm. Irradiation shifted the concentration-growth inhibition curves of PHOTOCYANINE to the left and decreased the IC(50)s of PHOTOCYANINE required to produce equivalent inhibition by 200-fold on various cell lines. The amphipathic PHOTOCYANINE permeated through HepG2 cell membrane and predominately distributed to lysosome and mitochondria, where it significantly reduced mitochondrial membrane potential (Delta Psi m) and increased caspase-3 activity in a concentration-dependent manner after irradiation. Early apoptosis of HepG2 occurred followed by necrosis when concentrations of PHOTOCYANINE were increased in the presence of irradiation. Reactive oxygen species (ROS) production was significant following PHOTOCYANINE plus irradiation treatment and cell cycle was mainly arrested at G(2)/M stage. In conclusion, PHOTOCYANINE, once irradiated, induces HepG2 cells into apoptosis via reducing DWm, producing ROS, activating caspase-3, and causing cell arrest at G(2)/M stage. This study provides important insights into molecular mechanisms of the anti-cancer PHOTOCYANINE, which now is being applied for in the clinical trials II in China. Published by Elsevier Ltd.
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