Immunomodulatory Effect of Arctigenin, a Lignan Compound, on Tumour Necrosis Factor-α and Nitric Oxide Production, and Lymphocyte Proliferation

Cho, Jae Youl; Kim, Ae Ra; Yoo, Eun Sook; Baik, Kyong Up; Park, Myung Hwan

doi:10.1211/0022357991777001

Cited by 73 publications

(48 citation statements)

References 26 publications

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“…Arctigenin has also been reported to modulate immunologic responses (25) and to induce apoptosis in colon cancer cell lines (22). Therefore, the mechanism of antitumor activity of this agent may not be simple and the results of the present study suggest the involvement of the Akt pathway.…”

Section: Discussionmentioning

confidence: 69%

Identification of Arctigenin as an Antitumor Agent Having the Ability to Eliminate the Tolerance of Cancer Cells to Nutrient Starvation

Awale¹,

Lü²,

Kalauni³

et al. 2006

Cancer Research

309

337

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Tumor cells generally proliferate rapidly and the demand for essential nutrients as well as oxygen always exceeds the supply due to the unregulated growth and the insufficient and inappropriate vascular supply. However, cancer cells show an inherent ability to tolerate extreme conditions, such as that characterized by low nutrient and oxygen supply, by modulating their energy metabolism. Thus, targeting nutrientdeprived cancer cells may be a novel strategy in anticancer drug development. Based on that, we established a novel screening method to discover anticancer agents that preferentially inhibit cancer cell viability under the nutrientdeprived condition. After screening 500 medicinal plant extracts used in Japanese Kampo medicine, we found that a CH 2 Cl 2 -soluble extract of Arctium lappa exhibited 100% preferential cytotoxicity under the nutrient-deprived condition at a concentration of 50 Mg/mL with virtually no cytotoxicity under nutrient-rich condition. Further bioassayguided fractionation and isolation led to the isolation of arctigenin as the primary compound responsible for such preferential cytotoxicity; the compound exhibited 100% preferential cytotoxicity against nutrient-deprived cells at a concentration of 0.01 Mg/mL. Furthermore, arctigenin was also found to strongly suppress the PANC-1 tumor growth in nude mice, as well as the growth of several of the tested pancreatic cancer cell lines, suggesting the feasibility of this novel antiausterity approach in cancer therapy. Further investigation of the mechanism of action of arctigenin revealed that the compound blocked the activation of Akt induced by glucose starvation, which is a key process in the tolerance exhibited by cancer cells to glucose starvation.

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Section: Discussionmentioning

confidence: 69%

Identification of Arctigenin as an Antitumor Agent Having the Ability to Eliminate the Tolerance of Cancer Cells to Nutrient Starvation

Awale¹,

Lü²,

Kalauni³

et al. 2006

Cancer Research

309

337

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show abstract

“…Arctigenin is the main active ingredient in Fructus arctii (Cho et al, 1999). Takasaki et al (2000) showed antitumor effects of both arctiin and arctigenin in suppression of mouse skin cancer, which was obtained from the aerial part of Saussurea medusaas.…”

Section: Discussionmentioning

confidence: 99%

Arctigenin Anti‐Tumor Activity in Bladder Cancer T24 Cell Line Through Induction of Cell‐Cycle Arrest and Apoptosis

Yang

Xiao

et al. 2012

The Anatomical Record

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Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose-and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 lmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer. Anat

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“…Par ailleurs, si l'on se réfère aux expérimen-tations tant in vitro que chez l'animal [4], ainsi qu'à des données épidémiologiques [5], ces actions résulte-raient de leurs propriétés phyto-oestrogènes. En effet, le sécoisolaricirésinol et le matairésinol sont métaboli-sés par les bactéries de la flore intestinale des mammifères en entérolignanes, respectivement l'entérodiol et l'entérolactone ( Figure 1B).…”

Section: Rôle Des Propriétés Phyto-oestrogènes Des Lignanesunclassified

Intérêt des lignanes dans la prévention et le traitement de cancers

et al. 2008

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Immunomodulatory Effect of Arctigenin, a Lignan Compound, on Tumour Necrosis Factor-α and Nitric Oxide Production, and Lymphocyte Proliferation

Cited by 73 publications

References 26 publications

Identification of Arctigenin as an Antitumor Agent Having the Ability to Eliminate the Tolerance of Cancer Cells to Nutrient Starvation

Identification of Arctigenin as an Antitumor Agent Having the Ability to Eliminate the Tolerance of Cancer Cells to Nutrient Starvation

Arctigenin Anti‐Tumor Activity in Bladder Cancer T24 Cell Line Through Induction of Cell‐Cycle Arrest and Apoptosis

Intérêt des lignanes dans la prévention et le traitement de cancers

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