Potential of xanthones from tropical fruit mangosteen as anti-cancer agents: caspase-dependent apoptosis induction in vitro and in mice.
The pericarp of mangosteen (Garcinia mangostana L.) is rich in various xanthones that are known to possess unique biological activities. In this work, we characterized the anti-proliferative and cytotoxic activities of mangosteen xanthones both in vitro and in mice. In vitro analysis with a human colorectal adenocarcinoma cell line, COLO 205, showed that mangosteen xanthones not only inhibit the proliferation of target cells but also induce their death by apoptosis that involves the activation of the caspase cascade. In vivo analysis using a mouse subcutaneous tumor model with COLO 205 cells showed that, at relatively low doses, the growth of tumors was repressed upon intratumoral administration of mangosteen xanthones. When a higher dose of mangosteen xanthones was administered, the size of tumors was reduced gradually, and, in some mice, the disappearance of tumors was seen. Histopathological evaluation and biochemical analysis of tumors that received mangosteen xanthones indicate the induction of apoptosis in tumors, which resulted in the repression of their growth and the reduction of their sizes. These results demonstrate the potential of mangosteen xanthones to serve as anti-cancer agents for the chemotherapy of cancer.
Watanapokasin
Ramida
R
Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand. ramidawa@yahoo.com
Jarinthanan
Faongchat
F
Jerusalmi
Alan
A
Suksamrarn
Sunit
S
Nakamura
Yukio
Y
Sukseree
Supawadee
S
Uthaisang-Tanethpongtamb
Wanlaya
W
Ratananukul
Piniti
P
Sano
Takeshi
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D004789:Enzyme Activation; D005260:Female; D005638:Fruit / Q000737:chemistry; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D044004:Xanthones; D020169:Caspases