TY - JOUR
T1 - In vitro and in vivo antitumor activity of a novel hypocrellin B derivative for photodynamic therapy
AU - Zhao, Hongyou
AU - Yin, Rong
AU - Chen, Defu
AU - Ren, Jie
AU - Wang, Yucheng
AU - Zhanga, Jiaying
AU - Deng, Hong
AU - Wang, Ying
AU - Qiu, Haixia
AU - Huang, Naiyan
AU - Zou, Qianli
AU - Zhao, Jingquan
AU - Gu, Ying
PY - 2014/6
Y1 - 2014/6
N2 - Background: Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by irradiating photosensitizers with light exposure to produce reactive oxygen species (ROS). An ideal photosensitizer is a crucial element to PDT. In the current study, we evaluated the photodynamic activity of a novel photosensitizer, the derivative of hypocrellin B (HB), 17-(3-amino-1-pentanesulfonic acid)-substituted hypocrellin B Schiff-base (PENSHB), both in vitro and in vivo. Methods: Physicochemical characteristics of the novel photosensitizer were compared with that of its parent HB. The intracellular distribution of photosensitizers and mitochondrial membrane potential were detected with laser scanning confocal microscopy. The pathway of cell death was analyzed by flow cytometry. The release of proapoptotic proteins was evaluated by Western blot. S180 tumor model was used to evaluate the antitumor effects of PENHB-mediated PDT. Results: Compared with its parent HB, water solubility of the derivative was improved enormously (6.6. mg/ml vs. 4.6. μg/ml), rendering its intravenous injection feasible without auxiliary solvent. The derivative had better PDT effect than HB in vitro under similar dark cytotoxicity. Moreover, PENSHB-mediated PDT was able to induce mitochondrial inner membrane permeabilisation, cytochrome c release, caspase-3 activation and subsequent apoptotic death. In vivo study showed that more than half of tumor bearing mice were cured by PENSHB-mediated PDT. Conclusions: In vitro and in vivo studies suggest that PENSHB is an effective photosensitizer for PDT to tumors. Therefore, PENSHB as a novel photosensitizer has a good prospect of clinical application.
AB - Background: Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by irradiating photosensitizers with light exposure to produce reactive oxygen species (ROS). An ideal photosensitizer is a crucial element to PDT. In the current study, we evaluated the photodynamic activity of a novel photosensitizer, the derivative of hypocrellin B (HB), 17-(3-amino-1-pentanesulfonic acid)-substituted hypocrellin B Schiff-base (PENSHB), both in vitro and in vivo. Methods: Physicochemical characteristics of the novel photosensitizer were compared with that of its parent HB. The intracellular distribution of photosensitizers and mitochondrial membrane potential were detected with laser scanning confocal microscopy. The pathway of cell death was analyzed by flow cytometry. The release of proapoptotic proteins was evaluated by Western blot. S180 tumor model was used to evaluate the antitumor effects of PENHB-mediated PDT. Results: Compared with its parent HB, water solubility of the derivative was improved enormously (6.6. mg/ml vs. 4.6. μg/ml), rendering its intravenous injection feasible without auxiliary solvent. The derivative had better PDT effect than HB in vitro under similar dark cytotoxicity. Moreover, PENSHB-mediated PDT was able to induce mitochondrial inner membrane permeabilisation, cytochrome c release, caspase-3 activation and subsequent apoptotic death. In vivo study showed that more than half of tumor bearing mice were cured by PENSHB-mediated PDT. Conclusions: In vitro and in vivo studies suggest that PENSHB is an effective photosensitizer for PDT to tumors. Therefore, PENSHB as a novel photosensitizer has a good prospect of clinical application.
KW - Apoptosis
KW - Hypocrellin B derivative
KW - In vivo PDT activity
KW - Mitochondria
KW - PDT
UR - http://www.scopus.com/inward/record.url?scp=84901616398&partnerID=8YFLogxK
U2 - 10.1016/j.pdpdt.2014.01.003
DO - 10.1016/j.pdpdt.2014.01.003
M3 - Article
C2 - 24534694
AN - SCOPUS:84901616398
SN - 1572-1000
VL - 11
SP - 204
EP - 212
JO - Photodiagnosis and Photodynamic Therapy
JF - Photodiagnosis and Photodynamic Therapy
IS - 2
ER -