Obovatol inhibits colorectal cancer growth by inhibiting tumor cell proliferation and inducing apoptosis

Lee, Su-Kyung; Kim, Hye-Nan; Kang, Yeong-Rim; Lee, Chang Woo; Kim, Hwan‐Mook; Han, Dong Cho; Shin, Jongheon; Bae, KiHwan; Kwon, Byoung‐Mog

doi:10.1016/j.bmc.2008.08.033

Cited by 37 publications

(24 citation statements)

References 24 publications

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“…Previous studies showed various properties of obovatol such as anti-bacterial, anti-tumour and anti-platelet activities (Ito et al, 1982;Pyo et al, 2002;Lee et al, 2008). The anti-inflammatory activity of obovatol was also reported in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells (Choi et al, 2007).…”

Section: Introductionb Ph_659 16461662mentioning

confidence: 98%

Obovatol attenuates microglia‐mediated neuroinflammation by modulating redox regulation

Ock

Han

Hong

et al. 2010

British J Pharmacology

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Background and purpose: Obovatol isolated from the medicinal herb Magnolia obovata exhibits a variety of biological activities. Here, the effect of obovatol and its mechanism of action on microglial activation, neuroinflammation and neurodegeneration were investigated. Experimental approach: In microglial BV-2 cells stimulated with lipopolysaccharide (LPS), we measured nitric oxide (NO) and cytokine production, and activation of intracellular signalling pathways by reverse transcription-polymerase chain reaction and Western blots. Cell death was assayed in co-cultures of activated microglia (with bacterial LPS) and neurons and in LPS-induced neuroinflammation in mice in vivo. Key results: Obovatol inhibited microglial NO production with an IC50 value of 10 mM. Obovatol also inhibited microglial expression of proinflammatory cytokines and inducible nitric-oxide synthase, which was accompanied by the inhibition of multiple signalling pathways such as nuclear factor kappa B, signal transducers and activators of transcription 1, and mitogen-activated protein kinases. In addition, obovatol protected cultured neurons from microglial toxicity and inhibited neuroinflammation in mice in vivo. One molecular target of obovatol in microglia was peroxiredoxin 2 (Prx2), identified by affinity chromatography and mass spectrometry. Obovatol enhanced the reactive oxygen species (ROS)-scavenging activity of Prx2 in vitro, thereby suppressing proinflammatory signalling pathways of microglia where ROS plays an important role. Conclusions and implications:Obovatol is not only a useful chemical tool that can be used to investigate microglial signalling, but also a promising drug candidate against neuroinflammatory diseases. Furthermore, our results indicate that Prx2 is a novel drug target that can be exploited for the therapeutic modulation of neuroinflammatory signalling.

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Section: Introductionb Ph_659 16461662mentioning

confidence: 98%

Obovatol attenuates microglia‐mediated neuroinflammation by modulating redox regulation

Ock

Han

Hong

et al. 2010

British J Pharmacology

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“…7,8) Over the past few decades, much attention has been focused on natural products as potential sources of novel anticancer drugs. [9][10][11][12][13][14] The therapeutic application of apoptosis has currently been used as a model for developing anticancer drugs, 15) because many chemotherapeutic drugs have been shown to induce apoptosis in cancer cells. 16) Thus, the identification of potential chemotherapeutic agents using mechanism-based study holds great promise for elucidating mechanisms and devising more specific and effective treatments for cancer-related diseases.…”

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confidence: 99%

Induction of Apoptosis in Human Leukemia Cell (Jurkat) by Neolignans Isolated from Seeds of Licaria puchury-major

Uchiyama

Tabata

Nomura

et al. 2009

Biological & Pharmaceutical Bulletin

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Ethanol extract of the seeds of Licaria puchury-major, a Brazilian herbal medicine, was found to inhibit cell proliferation in human leukemia cell line (Jurkat) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Bioassay-guided fractionation of the active components led to the isolation of one phenylpropanoid (1) and ten neolignans (2-11). The apoptosis-inducing activity of the compounds showing cytotoxicity in Jurkat cells was assessed by flow cytometric analysis. Among the identified neolignans, compounds 3, 4, 6 and 7 which have similar molecular structures, showed apoptotic activity. To elucidate the mechanism of apoptosis induction by neolignans, intracellular caspase-3, -8 and -9 activity in Jurkat cells was evaluated. Compound 4 markedly elevated the activity of caspase-3 and -9.

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“…Therefore, anti-cancer agents that generally achieve therapeutic purposes by inducing apoptosis in cells sensitive to them are highly desirable. 24) On the other hand, our data showed that exposure of HepG2 cells to TBMS I for 24 h caused a shift of cell numbers in different phases of cell cycle. As TBMS I concentration increased from 0 to 30 mM, there were increasingly more cells in G2 phase and accompanied by a decreasing percentage of cells in G1 phase.…”

Section: Discussionmentioning

confidence: 56%

Natural Plant Extract Tubeimoside I Promotes Apoptosis-Mediated Cell Death in Cultured Human Hepatoma (HepG2) Cells

Wang

Deng

Zhong³

et al. 2011

Biological & Pharmaceutical Bulletin

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Hepatoma is one of the most prevalent malignant tumor types and the third leading cause of cancer-related death worldwide.1) Each year, approximately 550000 new cases of hepatoma are reported worldwide, representing more than 5% of all human cancers.2) The incidence is particularly high among Eastern Asian and African regions, 3) but also rapidly rising in other parts of the world such as the United States. 4)Despite the development and use of multimodality therapies including chemotherapy, the clinical outcome of hepatoma treatment remains unsatisfactory, with usually less than 7% of the 5-year overall survival rate, 5,6) This may be in part due to ineffectiveness of the currently available chemotherapeutic drugs. Therefore, novel effective chemotherapeutic agents are desired, particularly those derived from natural products because of their intrinsic advantages. 7,8) One such agent is tubeimoside I (TBMS I), a constituent isolated from tuber of Bolbostemma paniculatum (MAXIM.) FRANQUET (Cucurbitaceae) that has long been used as a traditional Chinese herbal medicine to treat a wide variety of illnesses including inflammation and snake venom. 9) In the early 1980's, TBMS I was isolated and identified as a triterpenoid saponin with a unique macrocyclic structure as shown in Fig. 1. 10,11) Subsequently, it has been shown that TBMS I could be a potent anti-tumor agent 12) by inducing apoptosis in a variety of human cancer cell lines including promyelocytic leukemia (HL-60) cells, 13) cervical cancer (HeLa) cells, 14) and nasopharyngeal carcinoma (CNE-2Z) cells.15) However, TBMS I so far has not been well studied for its anti-tumor activity against hepatoma, even though that TBMS I is known to preferentially distribute in the liver during in vivo metabolism, and thus might better target liver cancer, or hepatoma. 16)Therefore, we evaluated TBMS I for its cytotoxicity to cultured human hepatoma cells or normal liver cells, from HepG2 or L-02 cell lines, respectively. We also investigated apoptosis-associated molecular events as potential mechanisms responsible for the cytotoxic effect of TBMS I on HepG2 cells. We found that compared to normal L-02 cells, TBMS I could inhibit proliferation of HepG2 cells more potently, which was paralleled by induction of several important signaling pathways associated with apoptosis, suggesting that TBMS I may be a potent promoter of apoptosis-mediated cell death in HepG2 cells and thus a particularly good candidate

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Obovatol inhibits colorectal cancer growth by inhibiting tumor cell proliferation and inducing apoptosis

Cited by 37 publications

References 24 publications

Obovatol attenuates microglia‐mediated neuroinflammation by modulating redox regulation

Obovatol attenuates microglia‐mediated neuroinflammation by modulating redox regulation

Induction of Apoptosis in Human Leukemia Cell (Jurkat) by Neolignans Isolated from Seeds of Licaria puchury-major

Natural Plant Extract Tubeimoside I Promotes Apoptosis-Mediated Cell Death in Cultured Human Hepatoma (HepG2) Cells

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