It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol significantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation significantly suppressed lung metastasis and primary tumour growth. In addition, magnolol significantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion.
We investigated the inhibitory effect of Magnolia obovata Thunb. bark ethanol extracts on human fibrosarcoma HT-1080 cells invasion in a reconstituted basement membrane [Matrigel (MG)]. We found that the effective components of the bark ethanol extracts were magnolol and honokiol, two biphenyl compounds. The extracts, magnolol and honokiol, did not affect HT-1080 cells adhesion to MG, but did inhibit HT-1080 cells migration at a high concentration (100 microM). HT-1080 cells secrete matrix metalloproteinase (MMP)-9, which degrades the extracellular matrix as a part of the invasive process. Magnolol and honokiol inhibited the activity of MMP-9, which may have been responsible, in part, for the inhibition of tumor cell invasiveness.
HPLC chromatograms of MeOH extracts from a fruit body of the wild-grown P. linteus (natural fruit body), from cultivated fungus (cultivated fruit body), and from the cultured mycelia were compared. The extract prepared from the natural fruit bodies revealed a typical HPLC profile referred to as type 1 with a major peak corresponding to meshimakobnol A (1) together with two minor peaks of hypholomine B (3) and inoscavin A (4); the cultivated fruit bodies exhibited a profile referred to as type 2 with major peaks corresponding to 3 and 4 and a minor peak of 1, and the cultured mycelia showed a profile referred to as type 3 without any of these peaks. We also analyzed HPLC chromatograms of commercial products of P. linteus obtained in the markets. Most of the products claimed to be natural fruit bodies exhibited type 1 profiles, except for one product having an intermediate HPLC profile between type 1 and type 2. The products claimed to be cultivated fruit bodies and cultured mycelia revealed type 2 and type 3 profiles, respectively. The present results indicate that the HPLC chromatogram of the methanol extract of P. linteus can be used as a fingerprint to identify whether the product is from natural fruit bodies, cultivated fruit bodies, or cultured mycelia.
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