Anti-invasive effects of curcuminoid compounds from Curcuma aromatica Salisb. on murine colon 26-L5 carcinoma cells

ショウガ科に属する Curcuma aromatica Salisb. の根茎のクロロホルム抽出エキスから,化学構造の明らかな4種のクルクミンおよびその関連化合物:curcumin(CA-1),demethoxycurcumin(CA-2),5\u27-methoxycurcumin(CA-3),bisdemethoxycurcumin(CA-4)を分離した。これらの化合物を用いてマウス結腸癌細胞(colon 26-L5)に対する増殖,基底膜への浸潤,細胞運動に及ぼす効果について検討した。クルクミン(CA-1)とその関連化合物(CA-2,3 および4)は,細胞に対して傷害性を示さない10μMの濃度において,マウス結腸癌細胞の基底膜への浸潤を抑制した(それぞれ22.8,28.9,10.3および62.0%の抑制率)。この癌細胞の運動能に対しても同様の抑制効果が観察された。これらのクルクミン関連化合物の中で,CA-4は強い抑制活性を持ち,癌細胞の浸潤および運動能に対して濃度依存的な抑制効果を示した。このように,クルクミン関連化合物の芳香族環のhydroxyl基およびmethoxyl基が癌細胞の浸潤活性の発現と関係している可能性が示唆された。 Bioassay-directed fractionation of the active chloroform extract from the rhizomes of Curcuma aromatica Salisb. (Zingiberaceae) led to the isolation of four main curcuminoid constituents: curcumin (CA-1), demethoxycurcumin (CA-2), 5\u27-methoxycurcumin (CA-3) and bisdemethoxycurcumin (CA-4). This is the first report to describe the isolation of CA-3 from C. aromatica. The chemical structures of these compounds were determined on the basis of spectral analysis and their inhibitory effects on the proliferation, invasion and migration of murine colon 26-L5 adenocarcinoma cells were evaluated in vitro. Curcumin and its analogues (CA-2, 3 and 4), at the non-cytotoxic concentration of 10μM, inhibited the invasive ability of colon 26-L5 cells to the ranges of 22.8, 28.9, 10.3 and 62.0%, respectively. A similar effect of these constituents on the migration of colon 26-L5 cells was also observed. Among these curcuminoids, CA-4 showed the strongest activities, inhibiting both tumor cell invasion and migration in a concentration-dependent manner

Anti-invasive and anti-angiogenic activities of Curcuma sp. extracts

Extracts of a herbal plant, Curcuma sp. (Zingiberaceae), were investigated for their anticancer activities. The rhizome of this plant is used in Thai folk medicine to treat cancers and to promote wound healing. In the present study, we performed preliminary bioassays to assess the anti-invasive and anti-angiogenic activities of the methanol (MeOH) and ethyl acetate (EtOAc) extracts. We found that both extracts produced moderate cytotoxic effects against murine hepatocellular carcinoma CBO140C12 cells. Interestingly, the EtOAc extract exhibited remarkable inhibitory effects on the invasion and migration of tumor cells in vitro, and on the adhesion of tumor cells to various extracellular matrix proteins. Moreover, the EtOAc extract also inhibited the formation of tube-like structures by hepatic sinusoidal endothelial (HSE) cells cultured on Matrigel-coated substrate, suggesting its anti-angiogenic activity. Altogether, our preliminary results indicate that the EtOAc extract contains active constituents that could potentially be developed into anticancer agents. ショウガ科に属するCurcuma種の根茎の抽出エキスを用いて抗腫瘍活性を検討した。この植物の根茎はタイの伝統医学において,癌の治療や創傷治癒を促進するために使われている。本研究では,メタノール及び酢酸エチルの抽出エキスを用いて,癌細胞の増殖,浸潤及び血管新生に対する抑制作用について予備的検討を行った。両エキスは,in vitroにおけるマウスの肝細胞癌:CBO140C12細胞の増殖に対して軽度の抑制効果を示した。興味あることに,酢酸エチル抽出エキスは,癌細胞の浸潤能,運動能及び種々の細胞外マトリックス成分に対する接着能に対して顕著な抑制効果を示した。さらに,マウス肝類洞内皮細胞(HSE)のマトリジェル基質上での管腔様構造の形成の抑制,すなわち,血管新生の阻害活性が認められた。このように,Curcuma種の根茎の抽出エキスを用いた予備検討において,酢酸エチル抽出エキス中には抗腫瘍薬剤を開発するための有効な成分が含まれている可能性が示唆された。Century COE Program, Toyama Medical and Pharmaceutical Universit

Anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative and curcumin ethylenediamine manganese complex

We investigated the anti-angiogenic effect of curcumin, curcumin ethylenediamine derivative (curcumin ED) and curcumin ethylenediamine manganese complex (curcumin EDMn) through the inhibition of the formation of tube-like structures by human umbilical vascular endothelial cells (HUVEC). Curcumin, curcumin ED, curcumin EDMn did not show cytotoxicity to HUVEC at concentrations equal and lower than 10 μM. At the concentration of 10 μM,curcumin, curcumin ED and curcumin EDMn inhibited the tube formation by approximately 94%, 40% and 65%, respectively. These results suggest that curcumin ED and curcumin EDMn might be useful as anti-angiogenic drugs in addition to their anti-lipid peroxidase and superoxide dismutase activities as described in our previous studies. クルクミン(curcumin),クルクミン・エチレンジアミン誘導体(curcumin ED)及びそのマンガン複合体(curcumin EDMn)を用いて,ヒト臍帯静脈内皮細胞の管腔様構造の形成能を指標にして血管新生阻害効果を検討した。10μMのcurcumin, curcumin ED及びcurcumin EDMn は,管腔様構造の形成をそれぞれ94%,40%及び65%程度阻害した。これらの結果は,curcuminとともにcurcumin ED及びcurcumin EDMnが以前に報告した抗脂質過酸化作用やスーパーオキシドジスムターゼ活性を有することに加えて,血管新生の阻害薬として有効であることが示唆された。21st Century COE Program, Toyama Medical and Pharmaceutical Universit