Potential of Xanthones from Tropical Fruit Mangosteen as Anti-cancer Agents: Caspase-Dependent Apoptosis Induction In Vitro and in Mice |
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Authors: | Ramida Watanapokasin Faongchat Jarinthanan Alan Jerusalmi Sunit Suksamrarn Yukio Nakamura Supawadee Sukseree Wanlaya Uthaisang-Tanethpongtamb Piniti Ratananukul Takeshi Sano |
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Institution: | 1. Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand 2. Center for Molecular Imaging Diagnosis and Therapy and Basic Science Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA 3. Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand 4. Howard Hughes Medical Institute, Department of Orthopedic Surgery, Children’s Hospital, Boston, MA, 02115, USA
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Abstract: | 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. |
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