Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague–Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats

Hirose, Masao; Yamaguchi, Tsuyoshi; Chen, Lin; Kimoto, Naoya; Futakuchi, Mitsuru; Kono, Tetsuya; Nishibe, Sansei; Shirai, Tomoyuki

doi:10.1016/s0304-3835(00)00411-0

Cited by 102 publications

(48 citation statements)

References 28 publications

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“…Arctigenin and arctiin have been reported to inhibit heterocyclic amine-induced colon, pancreatic, and hepatic carcinogenesis in rats, whereas 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoyl phorbol-13-acetate induced mouse skin carcinogenesis (23,24). Arctigenin has also been reported to modulate immunologic responses (25) and to induce apoptosis in colon cancer cell lines (22).…”

Section: Discussionmentioning

confidence: 99%

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

305

332

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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: 99%

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

305

332

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“…Fructus arctii have been reported to have antimicrobial, antioxidant, and anti-inflammatory activities (Lin et al, 1996;Huang et al, 2010). Research on the chemical compositions of Fructus arctii has shown that the most active ingredient of Fructus arctii is arctigenin (C 21 H 24 O 6 with a molecular weight of 372.41), a phenylpropanoid dibenzylbutyrolactone lignan (Hirose et al, 2000;Cho et al, 2004;Huang et al, 2004). Because of its anti-cancer and anti-viral activities and low toxicity, Fructus arctii should be tested for chemoprevention of different cancers.…”

Section: Introductionmentioning

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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“…This tall member of the Astreraceae family has a fleshy, edible taproot that has been used as a medicinal herb in Asian cultures for many years [25]. Recently, its anticancer properties have come under closer scrutiny [26][27][28][29]. Further investigation by our group resulted in the identification of a novel bioreactive species.…”

Section: Introductionmentioning

confidence: 99%

The Natural Product NI-07, Is Effective Against Breast Cancer Cells While Showing No Cytotoxicity to Normal Cells

Gollahon¹

2011

TOBCANJ

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Abstract:With the exception of a few anticancer agents, most breast cancer chemotherapeutics currently used have devastating effects on normal cells. We investigated the effectiveness of the natural product NI-07, derived from Arctium lappa, to determine its killing potential on breast cancer cells and its cytotoxic effects in breast normal cells. The breast cancer cell lines HCC1419, MCF7, MDA-MB-231, MDA-MB-468, SKBR3, the normal mammary epithelial cell line HME 50 HT and the normal mammary fibroblast cell line CCD-1074sk were analyzed in concurrently treated cultures of NI-07, Taxol™ or Untreated. NI-07-treated and Taxol™ -treated cells were cultured for two weeks to assess cell resistance/recovery. Cell viability was determined by cell counts, Trypan Blue exclusion and microscopy. Additionally, cell viability and cytotoxicity were measured by XTT. Statistical significance (p 0.05) of NI-07 to Untreated or Taxol™ was first determined using Two-Way ANOVA. Identified significant differences were further analyzed by One-Way ANOVA and Tukey's test for honestly significant differences. The effect size of NI-07 compared to untreated or Taxol™ was determined using Cohen's d. Our results showed significant declines in cell viability occurring in NI-07-treated cancer cells after 48 hours of treatment in contrast to the more rapid effect of Taxol™ (<24h). Additionally, cancer cell recovery was less effective in NI-07 versus Taxol™. Furthermore, NI-07 showed no cytotoxicity in normal cells. This lack of cytotoxicity, coupled with its killing efficiency in cancer cells, suggests that NI-07 could potentially make a strong anti-cancer compound or neo-adjuvant to current chemotherapy-based treatments.

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Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague–Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats

Cited by 102 publications

References 28 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

The Natural Product NI-07, Is Effective Against Breast Cancer Cells While Showing No Cytotoxicity to Normal Cells

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