کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8446212 1547161 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of human hepatocellular carcinoma HepG2 by phthalocyanine photosensitiser PHOTOCYANINE: ROS production, apoptosis, cell cycle arrest
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Inhibition of human hepatocellular carcinoma HepG2 by phthalocyanine photosensitiser PHOTOCYANINE: ROS production, apoptosis, cell cycle arrest
چکیده انگلیسی
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 IC50s 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 (ΔΨm) 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 G2/M stage. In conclusion, PHOTOCYANINE, once irradiated, induces HepG2 cells into apoptosis via reducing ΔΨm, producing ROS, activating caspase-3, and causing cell arrest at G2/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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 48, Issue 13, September 2012, Pages 2086-2096
نویسندگان
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