PhytoScience - Science

 

Cancer - Invitro

 

Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. (Lung, Liver, other gastric)

1: Planta Med. 2002 Nov;68(11):975-9.
Ho CK, Huang YL, Chen CC.
Department of Medical Research & Education, Veterans General Hospital, Taipei, ROC.

Treatment of hepatocellular carcinomas (HCCs) with chemotherapy has generally been disappointing and it is most desirable to have more effective new drugs.

We extracted and purified 6 xanthone compounds from the rinds (peel) of the fruits of Garcinia mangostana L., using partitioned chromatography and then tested the cytotoxic effects of these compounds on a panel of 14 different human cancer cell lines including 6 hepatoma cell lines, based on the MTT method.

Several commonly used chemotherapeutic agents were included in the assay to determine the relative potency of the potential new drugs.

Our results have shown that one of the xanthone derivatives which could be identified as garcinone E has potent cytotoxic effect on all
HCC cell lines as well as on the other gastric and lung cancer cell lines included in the screen.

We suggest that garcinone E may be potentially useful for the treatment of certain types of cancer.

PMID: 12451486 [PubMed - indexed for MEDLINE]

 

Cancer - Invitro


Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line.


1: J Ethnopharmacol. 2004 Jan;90(1):161-6.
Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N.
Department of Microbiology, Faculty of Pharmacy, Mahidol University, Sri Ayudthaya Road,
Rajdhevee, Bangkok 10400, Thailand. pypmk@mahidol.ac.th

This study was designed to determine the antiproliferative, apoptotic and antioxidative properties of crude methanolic extract (CME) from the pericarp of Garcinia mangostana (family Guttiferae) using human breast cancer (SKBR3) cell line as a model system.

SKBR3 cells were cultured in the presence of CME at various concentrations (0-50 microg/ml) for 48 h and the percentage of cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-di phenyl tetrazolium bromide (MTT) assay. CME showed a dose-dependent inhibition of cell proliferation with ED(50) of 9.25+/- 0.64 microg/ml.

We found that antiproliferative effect of CME was associated with apoptosis on breast cancer cell line by determinations of morphological changes and oligonucleosomal DNA fragments. In addition, CME at various concentrations and incubation times were also found to inhibit ROS production.

These investigations suggested that the methanolic extract from the pericarp of Garcinia mangostana had strong antiproliferation, potent antioxidation and induction of apoptosis. Thus, it indicates that this substance can show different activities and has potential for cancer chemoprevention which were dose dependent as well as exposure time dependent.

PMID: 14698525 [PubMed - in process]

 

Cancer - Invitro

Anti-Cancer:Study shows that xanthones inhibit growth of breast cancer, kidney cancer and melanoma.

 

1: Bioorg Med Chem. 2002 Dec;10(12):3725-30.
Xanthones as inhibitors of growth of human cancer cell lines and their effects on the proliferation of human lymphocytes in vitro.

Pedro M, Cerqueira F, Sousa ME, Nascimento MS, Pinto M. Centro de Estudos de Quimica Organica, Fitoquimica e Farmacologia da Universidade do Porto,
Faculdade de Farmacia, Porto, Portugal. madalena@ff.up.pt

Twenty-seven oxygenated xanthones have been assessed for their capacity to inhibit in vitro the growth of three human cancer cell lines, MCF-7 (breast cancer), TK-10 (renal cancer) and UACC- 62 (melanoma). The effect of these xanthones on the proliferation of human T-lymphocytes was also evaluated.

Differences on their potency toward the effect on the growth of the human cancer cell lines as well as on the proliferation of human T-lymphocytes can be ascribed to the nature and positions of the substituents on the xanthonic nucleus.

PMID: 12413829 [PubMed - indexed for MEDLINE]

 

Cancer - Invitro

Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines

 

Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y.
Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. kmatsumoto@giib.or.jp

We examined the effects of six xanthones from the pericarps of mangosteen, Garcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60.

All xanthones displayed growth inhibitory effects. Among them, alpha-mangostin showed complete inhibition at 10 microM through the induction of apoptosis.

PMID: 12932141 [PubMed - indexed for MEDLINE]

 

Cancer - Invitro

Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells.

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Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y
Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan.

alpha-Mangostin, a xanthone from the pericarps of mangosteen (Garcinia mangostana Linn.), was evaluated for in vitro cytotoxicity against human colon cancer DLD-1 cells.

The number of viable cells was consistently decreased by the treatment with alpha-mangostin at more than 20 microM. The cytotoxic effect of 20 microM alpha-mangostin was found to be mainly due to apoptosis, as indicated by morphological findings.

Western blotting, the results of an apoptosis inhibition assay using caspase inhibitors, and the examination of caspase activity did not demonstrate the activation of any of the caspases tested. However, endonuclease-G released from mitochondria with the decreased mitochondrial membrane potential was shown.

The levels of phospho-Erk1/2 were increased in the early phase until 1h after the start of treatment and thereafter decreased, and increased again in the late phase. On the other hand, the level of phospho-Akt was sharply reduced with the process of apoptosis after 6h of treatment. Interestingly, the level of microRNA-143, which negatively regulates Erk5 at translation, gradually increased until 24h following the start of treatment.

We also examined the synergistic growth suppression in DLD-1 cells by the combined treatment of the cells with alpha-mangostin and 5-FU which is one of the most effective chemotherapeutic agents for colorectal adenocarcinoma. The co-treatment with alpha-mangostin and 5-FU, both at 2.5 microM, augmented growth inhibition compared with the treatment with 5 microM of alpha-mangostin or 5 microM 5-FU alone.

These findings indicate unique mechanisms of alpha-mangostin-induced apoptosis and its action as an effective chemosensitizer.

PMID: 17553685 [PubMed - indexed for MEDLINE]

 

Cancer - Invivo

Panaxanthone Isolated from Pericarp of Garcinia mangostana L. Suppresses Tumor Growth and Metastasis of a Mouse Model of Mammary Cancer.

 

Doi H, Shibata MA, Shibata E, Morimoto J, Akao Y, Iinuma M, Tanigawa N, Otsuki Y.
Anticancer Res. 2009 Jul;29(7):2485-95. PMID: 19596918 [PubMed - in process]

BACKGROUND: The antitumor growth and antimetastatic activity of panaxanthone (approximately 80% alpha-mangostin and 20% gamma-mangostin) were studied in a mouse metastatic mammary cancer model that produces a metastatic spectrum similar to that seen in human breast cancer.

MATERIALS AND METHODS: Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were subsequently treated with panaxanthone at 0, 2,500, or 5,000 ppm in their diet. In vitro studies were also conducted to evaluate the effects of alpha-mangostin, the main component of panaxanthone, on BJMC3879 cells.

RESULTS: In the in vivo study, tumor volumes were significantly suppressed in mice treated with 2,500 and 5,000 ppm panaxanthone in their diet. The multiplicity of lung metastasis was significantly lower in the 5,000 ppm group. Lymph node metastasis also tended to decrease in the 5,000 ppm group but not significantly. The antitumor effects of panaxanthone were associated with elevation of apoptotic cell death, antiproliferation (inhibition of PCNA) and antiangiogenesis (inhibition of microvessel density).

The in vitro study demonstrated that alpha-mangostin induced apoptosis, as evidenced by increased numbers of TUNEL-positive cells, elevated activities of caspases and a decrease in mitochondrial membrane potential, cell cycle arrest in the G(1)-phase and decreases in the cell population in the S- and G(2)/M-phases.

CONCLUSION: These results suggest that the observed antimetastatic activity of panaxanthone may be of clinical significance as adjuvant therapy in metastatic human breast cancer, and may also be useful as a chemopreventative of breast cancer development.

Cancer - Invivo

Inhibitory effects of crude alpha-mangostin, a xanthone derivative, on two different categories of colon preneoplastic lesions induced by 1, 2-dimethylhydrazine in the rat.

 

Nabandith V, Suzui M, Morioka T, Kaneshiro T, Kinjo T, Matsumoto K, Akao Y, Iinuma M, Yoshimi N.
Tumor Pathology Division, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.

The purpose of this study was to examine whether crude alpha-mangostin (a major xanthone derivative in mangosteen pericarp (Garcinia mangostana)) has short-term chemopreventive effects on putative preneoplastic lesions involved in rat colon carcinogenesis.

The crude preparation was obtained by simple recrystallization of an ethylacetate extract of mangosteen pericarps.

A total of 33 five-week-old male F344 rats were randomly divided into 5 experimental groups. Rats in groups 1-3 were given a subcutaneous injection of 1,2-dimethylhydrazine (DMH)(40 mg/kg body weight) once a week for 2 weeks.

Starting one week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 0.02% and 0.05% crude alpha-mangostin, respectively, for 5 weeks. Rats in group 4 also received the diet containing 0.05% crude alpha-mangostin, while rats in group 5 served as untreated controls. The experiment was terminated 5 weeks after the start.

Dietary administration of crude alpha-mangostin at both doses significantly inhibited the induction and/or development of aberrant crypt foci (ACF) (P<0.05 for 0.02% crude alpha-mangostin, P<0.01 for 0.05% crude alpha-mangostin), when compared to the DMH-treated group (group 1). Moreover, treatment of rats with 0.05% crude alpha-mangostin significantly decreased dysplastic foci (DF) (P<0.05) and beta-catenin accumulated crypts (BCAC) (P<0.05), to below the group 1 values. The proliferating cell nuclear antigen (PCNA) labeling indices of colon epithelium and focal lesions in groups 2 and 3 were also significantly lower than in group 1 and this effect occurred in a dose dependent manner of the crude alpha-mangostin.

This finding that crude alpha-mangostin has potent chemopreventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.

PMID: 15546251 [PubMed - indexed for MEDLINE]

 

Cancer - Invitro

Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line.

 

Moongkarndi P, Kosem N, Luanratana O, conniegsomboonkusol S, Pongpan N.
Department of Microbiology, Faculty of Pharmacy, Mahidol University, Rajdhevee, Sri Ayudthaya Rd, Bangkok 10400, Thailand. pypmk@mahidol.ac.th

Ethanolic extracts of selected nine Thai medicinal plants were tested for antiproliferative activity against SKBR3 human breast adenocarcinoma cell line using MTT assay.

Garcinia mangostana showed the most potent activity. However, all plant extracts showed activity in potential range for further investigation on cancer cells. Copyright 2004 Elsevier B.V.

PMID: 15158999 [PubMed - indexed for MEDLINE]

 

Cancer - Invivo

Alpha-mangostin induces Ca2+-ATPase-dependent apoptosis via mitochondrial pathway in PC12 cells.

 

Sato A, Fujiwara H, Oku H, Ishiguro K, Ohizumi Y.
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences,
Tohoku University, Sendai, Japan.

We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells. Among these compounds, alpha-mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC(50) value of 4 microM. Alpha-mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation).

The flow cytometric analysis indicated that this compound induced apoptosis in time-and concentration-dependent manners. Alpha-mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, alpha-mangostin inhibited the sarco(endo)plasmic reticulum Ca(2+)-ATPase markedly.

There was a correlation between the Ca(2+)-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH(2)-terminal kinase (JNK/SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with alpha-mangostin treatment.

These results suggest that alpha-mangostin inhibits Ca(2+)-ATPase to cause apoptosis through the mitochondrial pathway.

PMID: 15153648 [PubMed - indexed for MEDLINE]

 

Cancer - Invitro

Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana.

Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N, Suksamrarn A.
Department of Chemistry, Faculty of Science,
Srinakharinwirot University, Sukhumvit,
Bangkok, Thailand. sunit@swu.ac.th

Three new prenylated xanthones, mangostenones C (1), D (2), and E (3), together with 16 known xanthones 4-19, were isolated from the young fruit (7-week maturity stage) of Garcinia mangostana.

The structural elucidation of the new compounds was mainly established on the basis of 1D and 2D NMR and HR-MS spectroscopic analysis. Compound 1 showed cytotoxic properties against three human cancer cell lines, epidermoid carcinoma of the mouth (KB), breast cancer (BC-1), and small cell lung cancer (NCI-H187), with IC50 values of 2.8, 3.53, and 3.72 microg/ml, respectively.

Among the isolates, alpha-mangostin (12), the major metabolite, exhibited the most potent effects against the BC-1 cells with an IC50 value of 0.92 microg/ml, an activity greater than that of the standard drug ellipticine (IC50 = 1.46 microg/ml).

Compound 12 also showed the highest activity against KB cells, while gartanin (10) displayed the strongest activity against the NCI-H187 cells at the respective IC50 values of 2.08 microg/ml and 1.08 microg/ml.

PMID: 16508181 [PubMed - indexed for MEDLINE]

 

Cancer - Invivo

Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen).

Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD.
Division of Medicinal Chemistry and Pharmacognosy,
College of Pharmacy, The Ohio State University,
Columbus, Ohio 43210, USA.

As part of ongoing research on cancer chemopreventive agents from botanical dietary supplements, Garcinia mangostana L. (commonly known as mangosteen) was selected for detailed study.

Repeated chromatography of a CH2Cl2-soluble extract of the pericarp led to the isolation of two new highly oxygenated prenylated xanthones, 8-hydroxycudraxanthone G (1) and mangostingone [7-methoxy-2-(3-methyl-2-butenyl)-8-(3-methyl-2-oxo-3-butenyl)-1,3,6-trihydroxyxanthone, 2], together with 12 known xanthones, cudraxanthone G (3), 8-deoxygartanin (4), garcimangosone B (5), garcinone D (6), garcinone E (7), gartanin (8), 1-isomangostin (9), alpha-mangostin (10), gamma-mangostin (11), mangostinone (12), smeathxanthone A (13), and tovophyllin A (14).

The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis. Except for compound 2, which was isolated as a minor component, the antioxidant activities of all isolates were determined using authentic and morpholinosydnonimine-derived peroxynitrite methods, and compounds 1, 8, 10, 11, and 13 were the most active.

Alpha-mangostin (10) inhibited 7,12-dimethylbenz[alpha]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay with an IC50 of 1.0 microg/mL (2.44 microM).

PMID: 16536578 [PubMed - indexed for MEDLINE]

 

Updated - 16 July 2009