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Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages.
Phytomedicine. 2015 Jul 15; 22(7-8):759-67.P

Abstract

BACKGROUND

Tumor growth and metastasis have been closely associated with the M2 macrophage-induced activation of tumor-associated macrophages (TAMs).

PURPOSE

The antitumor and antimetastatic actions of xanthangelol and 4-hydroxyderricin on the role of M2 macrophages in the TAMs of highly metastatic osteosarcoma LM8-bearing mice have not yet been fully elucidated. In order to clarify the mechanisms underlying the antitumor and antimetastatic actions of the above chalcones, we performed in vivo and in vitro studies.

STUDY DESIGN

The antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin were examined in vivo and the effects on M2 macrophage differentiation and activation were examined in vitro.

METHODS

We examined the antitumor and antimetastatic effects of xanthoangelol and 4-hydroxyderricin on highly metastatic osteosarcoma LM8-bearing mice (in vivo). Further, we examined their effects on the differentiation of interleukin (IL)-4 plus IL-13-induced M2 macrophages and activation of IL-4 plus IL13-induced M2 macrophages (in vitro). We also investigated the expression and phosphorylation of signal transducer and activator of transcript 3 (Stat 3) in the differentiation process of M2-polarized macrophages (in vitro).

RESULTS

Xanthoangelol or 4-hydroxyderricin (25 or 50 mg/kg, twice daily) inhibited tumor growth, metastasis to the lung and liver, and TAM expression in tumors. In addition, xanthoangelol (10, 25 or 50 μM) and 4-hydroxyderricin (5, 10, 25 or 50 μM) inhibited the production of IL-10 and monocyte chemoattractant protein (MCP)-1 in M2-polarized macrophages. This result indicated that xanthoangelol and 4-hydroxyderricin inhibited the activation of M2 macrophages. Furthermore, xanthoangelol (5-50 μM) inhibited the phosphorylation of Stat 3 without affecting the expression of the Stat 3 protein in the differentiation process of M2 macrophages, which indicated that these chalcones inhibited the differentiation of M2 macrophages.

CONCLUSION

These findings suggested that the antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderrcin might be attributed to the regulated activated TAMs through the inhibition of activation and differentiation of M2 macrophages in the tumor microenvironment.

Authors+Show Affiliations

Division of Functional Histology, Department of Functional Biomedicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.Department of Pharmacognosy, Osaka University of Pharmaceutical Sciences, Takatsuki City, Osaka 569-1094, Japan.Department of Pharmacognosy, Osaka University of Pharmaceutical Sciences, Takatsuki City, Osaka 569-1094, Japan.Division of Biochemical Pharmacology, Department of Basic Medical Research, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan . Electronic address: yokim@m.ehime-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26141763

Citation

Sumiyoshi, Maho, et al. "Antitumor and Antimetastatic Actions of Xanthoangelol and 4-hydroxyderricin Isolated From Angelica Keiskei Roots Through the Inhibited Activation and Differentiation of M2 Macrophages." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 22, no. 7-8, 2015, pp. 759-67.
Sumiyoshi M, Taniguchi M, Baba K, et al. Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages. Phytomedicine. 2015;22(7-8):759-67.
Sumiyoshi, M., Taniguchi, M., Baba, K., & Kimura, Y. (2015). Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 22(7-8), 759-67. https://doi.org/10.1016/j.phymed.2015.05.005
Sumiyoshi M, et al. Antitumor and Antimetastatic Actions of Xanthoangelol and 4-hydroxyderricin Isolated From Angelica Keiskei Roots Through the Inhibited Activation and Differentiation of M2 Macrophages. Phytomedicine. 2015 Jul 15;22(7-8):759-67. PubMed PMID: 26141763.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages. AU - Sumiyoshi,Maho, AU - Taniguchi,Masahiko, AU - Baba,Kimiye, AU - Kimura,Yoshiyuki, Y1 - 2015/05/27/ PY - 2014/10/21/received PY - 2015/05/08/revised PY - 2015/05/13/accepted PY - 2015/7/5/entrez PY - 2015/7/5/pubmed PY - 2015/9/30/medline KW - Antimetastatic KW - Antitumor KW - Chalcones KW - M2 macrophage KW - Stat3 SP - 759 EP - 67 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 22 IS - 7-8 N2 - BACKGROUND: Tumor growth and metastasis have been closely associated with the M2 macrophage-induced activation of tumor-associated macrophages (TAMs). PURPOSE: The antitumor and antimetastatic actions of xanthangelol and 4-hydroxyderricin on the role of M2 macrophages in the TAMs of highly metastatic osteosarcoma LM8-bearing mice have not yet been fully elucidated. In order to clarify the mechanisms underlying the antitumor and antimetastatic actions of the above chalcones, we performed in vivo and in vitro studies. STUDY DESIGN: The antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin were examined in vivo and the effects on M2 macrophage differentiation and activation were examined in vitro. METHODS: We examined the antitumor and antimetastatic effects of xanthoangelol and 4-hydroxyderricin on highly metastatic osteosarcoma LM8-bearing mice (in vivo). Further, we examined their effects on the differentiation of interleukin (IL)-4 plus IL-13-induced M2 macrophages and activation of IL-4 plus IL13-induced M2 macrophages (in vitro). We also investigated the expression and phosphorylation of signal transducer and activator of transcript 3 (Stat 3) in the differentiation process of M2-polarized macrophages (in vitro). RESULTS: Xanthoangelol or 4-hydroxyderricin (25 or 50 mg/kg, twice daily) inhibited tumor growth, metastasis to the lung and liver, and TAM expression in tumors. In addition, xanthoangelol (10, 25 or 50 μM) and 4-hydroxyderricin (5, 10, 25 or 50 μM) inhibited the production of IL-10 and monocyte chemoattractant protein (MCP)-1 in M2-polarized macrophages. This result indicated that xanthoangelol and 4-hydroxyderricin inhibited the activation of M2 macrophages. Furthermore, xanthoangelol (5-50 μM) inhibited the phosphorylation of Stat 3 without affecting the expression of the Stat 3 protein in the differentiation process of M2 macrophages, which indicated that these chalcones inhibited the differentiation of M2 macrophages. CONCLUSION: These findings suggested that the antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderrcin might be attributed to the regulated activated TAMs through the inhibition of activation and differentiation of M2 macrophages in the tumor microenvironment. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/26141763/Antitumor_and_antimetastatic_actions_of_xanthoangelol_and_4_hydroxyderricin_isolated_from_Angelica_keiskei_roots_through_the_inhibited_activation_and_differentiation_of_M2_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(15)00117-8 DB - PRIME DP - Unbound Medicine ER -