Apigenin Induces Apoptosis through Mitochondrial Dysfunction in U‑2 OS Human Osteosarcoma Cells and Inhibits Osteosarcoma Xenograft Tumor Growth in Vivo

The cytostatic drug from natural products has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Apigenin, a type of flavonoid, exhibits anticancer actions, but there is no report to show that apigenin induced apoptosis in osteosarcoma cells. The aim of this study was...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2012-11, Vol.60 (45), p.11395-11402
Main Authors: Lin, Chin-Chung, Chuang, Ya-Ju, Yu, Chien-Chih, Yang, Jai-Sing, Lu, Chi-Cheng, Chiang, Jo-Hua, Lin, Jing-Pin, Tang, Nou-Ying, Huang, An-Cheng, Chung, Jing-Gung
Format: Article
Language:English
Subjects:
Animals
anticarcinogenic activity
Antineoplastic Agents, Phytogenic - pharmacology
apigenin
Apigenin - pharmacology
apoptosis
Apoptosis - drug effects
Biological and medical sciences
Bone Neoplasms - drug therapy
Bone Neoplasms - metabolism
Bone Neoplasms - physiopathology
caspase-3
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
cell viability
cytotoxicity
Down-Regulation - drug effects
drugs
flow cytometry
Food industries
Fundamental and applied biological sciences. Psychology
Humans
immunoblotting
Male
membrane potential
Mice
Mice, Inbred BALB C
Mice, Nude
Mitochondria - drug effects
Mitochondria - metabolism
osteosarcoma
Osteosarcoma - drug therapy
Osteosarcoma - metabolism
Osteosarcoma - physiopathology
proteins
Xenograft Model Antitumor Assays
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Summary:The cytostatic drug from natural products has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Apigenin, a type of flavonoid, exhibits anticancer actions, but there is no report to show that apigenin induced apoptosis in osteosarcoma cells. The aim of this study was to investigate the effects of apigenin on U-2 OS human osteosarcoma cells and clarify that the apigenin-induced apoptosis-associated signals. The cytotoxic effects of apigenin were examined by culturing U-2 OS cells with or without apigenin. The percentage of viable cells via PI staining, apoptotic cells, productions of ROS and Ca2+, and the level of mitochondrial membrane potential (ΔΨm) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by immunoblotting. Results indicated that apigenin significantly decreased cell viability. Apigenin effectively induced apoptosis through the activations of caspase-3, -8, -9, and BAX and promoted the release of AIF in U-2 OS cells. In nude mice bearing U-2 OS xenograft tumors, apigenin inhibited tumor growth. In conclusion, apigenin has anticancer properties for induction of cell apoptosis in U-2 OS cells and suppresses the xenograft tumor growth. These findings offer novel information that apigenin possibly possesses anticancer activity in human osteosarcoma.
ISSN:0021-8561
1520-5118
DOI:10.1021/jf303446x