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 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.
Department of Chinese Medicine, Fong-Yuan Hospital, Department of Health, Executive Yuan, Taichung 420, Taiwan.
Chin-Chung
CC
Lin
Ya-Ju
YJ
Chuang
Chien-Chih
CC
Yu
Jai-Sing
JS
Yang
Chi-Cheng
CC
Lu
Jo-Hua
JH
Chiang
Jing-Pin
JP
Lin
Nou-Ying
NY
Tang
An-Cheng
AC
Huang
Jing-Gung
JG
Chung
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D047310:Apigenin