Ichthyotoxic and Anticarcinogenic Effects of Triterpenoids from Sandoricum koetjape Bark

Ismail, Intan Safinar; Ito, Hideyuki; Mukainaka, Teruo; Higashihara, Hiroshi; Enjo, Fumio; Tokuda, Harukuni; Nishino, Hoyoku; Yoshida, Takashi

doi:10.1248/bpb.26.1351

Cited by 31 publications

(21 citation statements)

References 20 publications

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“…Many studies have been focused on screening novel non-cytotoxic compounds or extracts from natural products but have antiangiogenic properties [13,14]. KA has found to have antibacterial, anti-inflammatory, anti-tumor promoting activity and DNA polymerase inhibition properties [9,15-17]. Till now, there are no reports about antiangiogenic activity of KA.…”

Section: Discussionmentioning

confidence: 99%

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Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

et al. 2011

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BackgroundAngiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.ResultsTreatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC50 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.ConclusionsThe non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.

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Section: Discussionmentioning

confidence: 99%

“…KA was found to have poor cytotoxicity on a number of human cancer cell lines and murine lymphocytic leukemia [7]. KA was also shown to have ichthyotoxic and chemopreventive effects [9]. In this study, an attempt has been made to investigate the antiangiogenic activity of KA in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

et al. 2011

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“…Oleanolic acid (83), 3-acetoxy-oleanolic acid (84), and katononic acid (90) all inhibited TPA-induced EBV-EA (Ohigashi et al, 1986;Konoshima et al, 1987;Taniguchi et al, 2002;Ismail et al, 2003;Banno et al, 2004); 84 was more active than 83, and 90 was less active. Oleanolic acid (83) was a good inhibitor of the mutagenicity of benzo[a]pyrene in a bacterial assay (Niikawa et al, 1993).…”

Section: Cancermentioning

confidence: 99%

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

et al. 2007

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Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook. f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

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“…Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape and was found to have mild cytotoxicity on a number of human cancer cell lines and murine lymphocytic leukemia (7,9). KA has been found to have anti-bacterial, anti-inflammatory, anti-tumor promoting activity and DNA polymerase inhibition properties (10)(11)(12)(13). In this study, an attempt has been made to understand the cellular and molecular mechanisms involved in cytotoxic effects of KA towards colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Koetjapic acid, a natural triterpenoid, induces apoptosis in colon cancer cells

et al. 2011

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Abstract. Deregulated cell signaling pathways result in cancer development. More than one signal transduction pathway is involved in colorectal cancer pathogenesis and progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene triterpene isolated from the Sandoricum koetjape stem bark. We report the cellular and molecular mechanisms of anticancer activity of KA towards human colorectal cancer. The results showed that KA induces apoptosis in HCT 116 colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic caspases. We confirmed that KA-induced apoptosis was mediated by DNA fragmentation, nuclear condensation and disruption in the mitochondrial membrane potential. Further studies on the effect of KA on cancer pathways show that the compound causes down-regulation of Wnt, HIF-1α, MAP/ERK/JNK and Myc/Max signaling pathways and up-regulates the NF-κB signaling pathway. The result of this study highlights the anticancer potential of KA against colorectal cancer.

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Ichthyotoxic and Anticarcinogenic Effects of Triterpenoids from Sandoricum koetjape Bark

Cited by 31 publications

References 20 publications

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

Koetjapic acid, a natural triterpenoid, induces apoptosis in colon cancer cells

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