Preferential target is mitochondria in α-mangostin-induced apoptosis in human leukemia HL60 cells

Matsumoto, Kenji; Akao, Yukihiro; Yi, Hong; Ohguchi, Ken-ichi; Ito, Tetsuro; Tanaka, Toŝhiyuki; Kobayashi, Eizaburo; Iinuma, Munekazu; Nozawa, Yoshinori

doi:10.1016/j.bmc.2004.08.034

Cited by 186 publications

(123 citation statements)

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“…Furthermore, the apoptosis activity also depends on the number of free hydroxyl groups. 7,9,10) Pyranoxanthones, produced naturally or synthetically from 1 by acid-catalysed cyclisation of the prenyl group, have been found to have reduced cytotoxic potency compared with 1. 9) For 3,6-di-O-alkylated a-mangostin, the inhibitory effects on antifungal activity were reduced dramatically as compared with a-mangostin.…”

mentioning

confidence: 99%

Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of .ALPHA.-Mangostin

Hansen

Vang

et al. 2009

Chem. Pharm. Bull.

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Xanthones are widely distributed in the genus Garcinia (Guttiferae), which provides compounds with a wide range of pharmacological effects such as cytotoxic, anti-bacterial, antioxidant and anti-human immunodeficiency virus (HIV) activities.1-3) The diverse substitution patterns of xanthones provide a good basis for different biological activity and for structure-activity relationship studies. 4)a-Mangostin (1), the dominating constituent of the fruit hulls of Garcinia mangostana, together with b-mangostin (2) and g-mangostin (3) (Fig. 1), have exhibited various biological activities, such as cytotoxicity in different cell lines together with anti-oxidative, anti-inflammatory, and anti-bacterial activities.5) As examples, inhibition of the cell proliferation of DLD-1 cells by 1 was observed at concentrations above 2 mM with an IC 50 value at 7.5 mM.6) This value corresponds to the activity observed in HL-60 cells.7) 3 seems to have a stronger effect compared with 1 and 2 8) but this is not confirmed by all reports. [7][8][9] Besides their slightly different potencies, three mangostins (1-3) differ in their mechanism of action. 3 caused accumulation of the cells in S-phase, whereas the cells treated with 1 and 2 showed G 0 /G 1 accumulation. Furthermore, the three mangostins (1-3) showed different expression profiles for proteins involved in the cell cycle regulation.8) The cytotoxic activity of 1 is only partly explained by apoptosis, as higher concentrations are needed for apoptosis than necessary for cytotoxicity.6) Apoptosis seems to be caused by 1-induced dysfunction of mitochondria. 10)Beside 1-3, several other xanthones have been tested for their cytotoxic activity and a structure-activity relationship can partly be elucidated. In all such experiments, the mangostins showed the strongest effect.7-9) Analysis of the cytotoxic effect of 6-methoxy-b-mangostin 8) indicated that the free hydroxyl group at C-6 was necessary for the cytotoxic activity. Furthermore, the apoptosis activity also depends on the number of free hydroxyl groups. 7,9,10) Pyranoxanthones, produced naturally or synthetically from 1 by acid-catalysed cyclisation of the prenyl group, have been found to have reduced cytotoxic potency compared with 1. 9) For 3,6-di-O-alkylated a-mangostin, the inhibitory effects on antifungal activity were reduced dramatically as compared with a-mangostin.11) However, the cytotoxic effects of these derivatives on MCF-7 cells (human breast cancer cells) or DLD-1 (human colon cancer cells) have not been investigated yet.In this paper, we report the isolation of two new geranylated xanthones (4, 5) and five known compounds (2, 6-9) from the bark of Garcinia oliveri PIERRE, a Vietnamese tall tree whose young buds and sour fruit are used for soup cooking. However, no use in folk medicine nor identification of specific compounds has been previously reported.12) Furthermore, conversion of a-mangostin into O-alkylated a-mangostin derivatives (10-17) is described. Cytotoxic activity for compounds 1-3 and 6-17 was analy...

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confidence: 99%

Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of .ALPHA.-Mangostin

Hansen

Vang

et al. 2009

Chem. Pharm. Bull.

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“…Numerous studies have also documented the anticancer effects of xanthones isolated from G. mangostana fruit pericarp. Several xanthones including α, β and γ mangostin, mangostinone, 2-iosprenyl-1,7-dihydroxy-3-methoxy xanthone and garcinone E exhibit anti-proliferative [48] and apoptotic properties 49 against human leukemia cell line HL60. Garcinone E has also been reported to have potent cytotoxic effects on HCC36, TONG, HA22T, Hep3B, HEpG2 and SK-Hep-1 hepatocarcinoma cell lines 50 .…”

Section: Discussionmentioning

confidence: 99%

An examination of the antimicrobial and anticancer properties of Garcinia cambogia fruit pericarp extracts

Hart

Cock

2016

BEMS Reports

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Background:Garcinia cambogia (synonym Garcinia gummi-gutta) is commonly known as brindleberry and Malabar tamarind. It has received considerable recent interest due to its potential in the prevention and treatment of obesity and obesity related diseases. The fruit pericarp also has traditional uses in the treatment of a wide variety of diseases and medical conditions, yet these have received relatively little investigation to date. Methods: Garcinia cambogia fruit extracts were investigated for their ability to inhibit the growth of a panel of bacteria of medicinal importance. The extracts were also tested for their ability to block the proliferation of the CaCo 2 and HeLa human carcinoma cell lines. Results: Garcinia cambogia methanolic, aqueous and ethyl acetate extracts displayed broad spectrum antimicrobial activity, inhibiting the growth of between 16 (64 %; ethyl acetate extract) and 22 (88 % aqueous extract) of the 25 bacterial species tested. Strong inhibitory activity was detected with minimum inhibitory concentration (MIC) values <1000 µg/ml against many bacteria. All extracts were effective against both Gram negative and Gram positive bacteria, although Gram negative bacteria were more sensitive. All extracts displayed anti-proliferative activity against CaCo 2 and HeLa carcinoma cells, yet were non-toxic in the Artemia franciscana bioassay, with LC50 values greatly in excess of 1000 µg/ml. Conclusion: The inhibitory bioactivity against a range of microbes, the anti-proliferative activity against CaCo 2 and HeLa cells, as well as the lack of toxicity, indicate the potential for G. cambogia in the discovery and development of new natural pharmaceuticals.

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“…HCT 116 was selected because it was previously reported as a model of invasive and metastatic colon cancer (Rajput et al, 2008). α-mangostin was selected as a positive control because it is the main constituent of the extract and it was reported previously as apoptotic compound (Matsumoto et al, 2004;Matsumoto et al, 2003). Betulinic acid was selected as positive control for the cytotoxicity study because it is a cytotoxic compound from natural origin.…”

Section: Discussionmentioning

confidence: 99%

“…α-mangostin was the first xanthone isolated from G. mangostana and several other xanthones were isolated as well (Pedraza-Chaverri et al, 2008). Previous studies on different xanthones demonstrated remarkable pharmacological activities including analgesic (Cui et al, 2010), antioxidant (Jung et al, 2006), antiinflammatory Tewtrakul et al, 2009), anticancer (Akao et al, 2008;Doi et al, 2009;Hung et al, 2009;Matsumoto et al, 2004), antiallergy (Nakatani et al, 2002), antibacterial (Chomnawang et al, 2009;Sakagami et al, 2005), antituberculosis (Suksamrarn et al, 2003), antifungal (Kaomongkolgit et al, 2009) and antiviral (Chen et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Antitumorigenicity of xanthones-rich extract from Garcinia mangostana fruit rinds on HCT 116 human colorectal carcinoma cells

Aisha¹,

Abu‐Salah²,

Nassar³

et al. 2011

Rev. bras. farmacogn.

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This study aimed to investigate the antitumorigenicity of xanthones-rich extract from Garcinia mangostana L., Clusiaceae, fruit rinds which was obtained by a simple recrystallization of 75% ethanolic extract. α-Mangostin content of the extract was determined qualitatively by TLC and quantitatively by HPLC, and total xanthones content was quantified by UV spectrophotometry. The extract was evaluated for cytotoxicity, apoptosis and antitumorigenicity on HCT 116 human colorectal carcinoma cells. α-Mangostin was found to be the main constituent of the extract which was 71.2±0.1%, and the total xanthones content was 95±4.8% (wt/ wt). The extract showed potent dose dependent cytotoxicity with IC50 value 9.2 µg/ mL. Apoptosis studies revealed activation of caspases 3 and 7, DNA fragmentation, chromatin condensation and loss of mitochondrial membrane potential. Studies on cell migration and colony formation indicate reduced cell migration ability and clonogenicity of treated HCT 116 cells at sub-inhibitory concentrations. Taken together, the cytotoxic effect of the xanthones extract is mediated through the mitochondrial pathway of apoptosis. The reduced cell migration and clonogenicity of HCT 116 cells might prevent both primary and metastatic tumor growth in vivo which will be the topic of our future work using the metastatic orthotopic colon cancer model.

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Preferential target is mitochondria in α-mangostin-induced apoptosis in human leukemia HL60 cells

Cited by 186 publications

References 19 publications

Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of .ALPHA.-Mangostin

Cytotoxic Geranylated Xanthones and O-Alkylated Derivatives of .ALPHA.-Mangostin

An examination of the antimicrobial and anticancer properties of Garcinia cambogia fruit pericarp extracts

Antitumorigenicity of xanthones-rich extract from Garcinia mangostana fruit rinds on HCT 116 human colorectal carcinoma cells

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