title: Inhibition of breast cancer cell proliferation by a newly developed photosensitizer chrolophyll derivative CPD4.
abstract: To investigate the mechanism of inhibition of breast cancer cell proliferation by a newly developed photosensitizer chrolophyll derivative CPD4. MCF-7 cells were treated with CPD4 in different concentrations for 2 h, followed by irradiation (670 nm, 10 J/cm(2)) using a semiconductor laser. Apoptotic mode and ratio of treated cells were analyzed. Subcellular localization of CPD4 were observed. Mitochondrial membrane potential was measured, and expression of Bcl-2 and Bax was detected. Four groups were set in this study: (1) no photosensitizer or light irradiation treatment, (2) photosensitizer (2.5 μg/mL CPD4) alone, (3) light irradiation alone, and (4) combined photosensitizer and light irradiation treatment (2.5 μg/mL CPD4-PDT). Flow cytometry assays revealed that apoptotic ratio of CDP4-PDT treated cells increased significantly in a CDP4 dose-dependent manner whereas apoptotic and necrotic ratio in the control group was only 4.9%-6.2% and 1.3%-2.9%, respectively. CPD4 was primarily distributed in mitochondria. While no significant difference in mitochondrial membrane potential was observed among three control groups (BG, PG and IG group) (P<0.05), mitochondrial membrane potential in CDP4-PDT group decreased significantly after irradiation treatment (P>0.05). A simutanous downregulation of Bcl-2 protein and overexpression of Bax protein in CDP4-PDT treated cells led to a reduction in the Bcl-2/Bax ratio. CPD4 photodynamic treatment induced decreased mitochondrial membrane potential, and might thereby trigger apoptosis through mitochondrial pathway in MCF-7 cells. The treatment stimulated Bcl-2 expression but down-regulated Bax expression, which might suggest an alternative mechanism of apoptotic effect of CPD4.
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University 79 Guhuai Road, Jining 272000, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University 79 Guhuai Road, Jining 272000, China.
authors.forename: Junye
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University 79 Guhuai Road, Jining 272000, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University 79 Guhuai Road, Jining 272000, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, Affiliated Hospital of Jining Medical University 79 Guhuai Road, Jining 272000, China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Li
keywords: Chrolophyll derivative CPD4; apoptosis; breast cancer; mitochondrial membrane potential; photodynamic therapy