Fucoidan is a sulfated polysaccharide that is purified from brown algae, such as Fucus vesiculosus. This compound has multiple biological activities including immune-stimulating, and anti-viral activities. We recently demonstrated that the cytotoxicity of fucoidan can be dependent on the batch of its production and its molecular weight. In a previous study, fucoidan B exerted cytotoxicity toward mouse spleen cells. To confirm the biological activity of Fucoidan B, we cultured HL-60 cells, a human leukemia cell line, and treated then with fucoidan. The metabolic activity of the HL-60 cells decreased in response to treatment by fucoidan. Moreover, the morphology of HL-60 treated by fucoidan changed. To investigate the fucoidan’s effects, we analyzed the size and level of Annexin V/propidium iodide staining of HL-60 cells using a flow cytometer. Fucoidan consistently induced cell death, including apoptosis of HL-60 cells. As potential mechanisms, fucoidan destabilized the mitochondrial membrane potential and altered the production of reactive oxygen species in HL-60 cells. Taken together, these results suggest that fucoidan has anti-tumor activity on HL-60 cells via destabilization of mitochondrial membrane potential. The present study demonstrates that fucoidan can be used as an anti-cancer agent for leukemia.

Indirubin is the ac ti ve ingredi ent of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for t he t reatment of chronic myelocytic leukemia Here, we report that novel indirubin ,- 11‘ ivative‘ 5’ - nitro-indirubinoxime (5’ NIO) , has potent anti- proliferative activity on va rious human cancel‘ cells and oncogenic RK3E- ras rat kidney cells with ha lf- inhibi tory concentrati ons (1C50) ra nging from 1- 12 M, Treatment with indirubin derivative induced the activation 01' caspase 7 rollowed by apoptos is in RK3E- ras cells. lndirubin derivative showed strong anti-tumor activity in rat solid and oral tUll10r models , Direct inj ection of indirubin deri vative every other day for 10 days induced signifi cant inhi bition of tumor growth in Sprague-Dawley rats bearing RK3E- ras-induced tumors Histologically. t reatment with indiru bin de ri vative caused s ignifi cant inhi bit ion of tumor formation with increased apoptosis and decreased tumor cell prolife ration, These f indings provide the potent ial va lue of indirubin deri vative a s a novel candidate for ant i-tumor agents

lndil‘ ubin is the active ingredient of Danggui Longhui Wan‘ a mixture of herbal medici l1e t hat is used to treat chronic myelocytic leukemia in tradi t ional Chinese medicine‘ He re, we show that new indirubin deri vatives 5' -ni tro-indirubinoxime, 5' -f1 uoro-indiru binoxime and 5’ -tri rnethylacetamino-i nd i 1'1.1 bi noxi me‘ have potent a n ti- proliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells with lC50 con centration ranging from 1-25 μ M, When the RK3E-ras cells were treated with indirubin derivatives for 24 h, the activity of caspase-3 and caspasc-7 was induccd followed by apoptosis , 011 the other hand, the activity of SAPK/JNK was inhi bited over the same period , lndirubin deri vatives a lso s howed strong ant i-tumor activity in rat s이 id and oral tumor models The inhibition of tlUl10r g:rowth was observed in animals beaJ‘ing RK3E-ras-induced turnor given subcutaneous dose of 100 mg/kg every other day for 10 days, Histologically, μeatment of indirubin derivatives caused significant inhibition of tumor formation associated wi th increased apoptosis and decreased proliferation of tumor cell s , These findings provide the potential value of indirubin derivatives as a novel candi date fOl 없l tJ -cancer agents ,

본 연구는 EA에 의한 대식세포의 활성화를 매개로 한 항암효과와 항암작용과 관련된 대식세포의 면역조절효과를 확인하였다. 연구 결과 EA에 의해 RAW264.7세포 및 peritoneal macrophage 모두에서 항암효과가 증가하였으며, 증가된 대식세포의 항암효과는 TLR4 signaling을 blocking하는 CLI-095을 함께 처리하였을 때 일부 감소되었다. 이는 EA에 의한 항암 효과가 부분적으로 TLR4를 경유하는 기전으로 나타나는 것을 의미한다. 또한, EA에 대한 대식세포의 NO 분비조절효과를 측정하였으며, EA는 대식세포의 NO 생성을 증가시켰으나, 인위적으로 염증을 유발시켜 NO를 과도하게 분비한 상태에서는 NO 분비를 오히려 억제시키는 결과를 나타내었다. 이와 같이 EA에 의한 NO조절에 대한 이중 효과는 인체에 면역증강과 항염증 효과라는 긍정적인 효과를 나타내는 방향으로 조절하고 있으므로 EA를 이용한 항암요법의 보조제 및 면역보조제로써의 활용에 유익할 것으로 사료된다. 향후 EA에 대한 항암 작용 및 NO 조절에서 세포내 신호전달 작용기전에 대한 심도 있는 연구가 진행되어야 할 것으로 보인다.

본 연구는 길경 사포닌 추출물(PGS)를 이용하여 대식세포의 면역조절능력을 평가하였으며, 탐식작용, 항암작용, 항염증 작용에 모두 유의적인 효과를 나타내었다. 특히, 본 연구에서는 농도의존적으로 매우 유의적이게 나타난 PGS의 항암작용 기전을 측정하기 위하여 암세포 독성 물질로 알려진 NO 분비량을 측정하였으며, PGS에 의해 NO의 생성을 증가함을 확인하였다. 또한, PGS가 NO 생성 억제제 NIL을 함께 처리하였을 때 항암효과가 나타나지 않게 됨을 재확인함으로써, PGS 10 μg/mL에서 나타낸 대식세포의 항암효과는 일부 NO 생성 및 분비에 의한 작용 기전임을 보여주었다. PGS의 면역조절작용 중 항염증효과 실험에서는 PGS가 염증환경에서 과도하게 분비된 NO를 다소 억제하는 경향을 보였으나, 항염증조절에서 대표적인 물질로 알려진 TNF-α 조절에는 효과를 나타내지 않았다. PGS가 염증환경에서의 TNF-α억제조절에는 영향을 미치지 않았으나 TNF-α는 항암물질로도 알려져 있으므로 향후 PGS의 항암효과에 대한 연구에서 TNF-α의 생성에 관한 연구는 NO를 매개하는 항암 효과 외에 다른 기전을 설명해줄 수 있을 것으로 보인다. 이러한 결과들은 PGS가 항암요법의 보조제 및 면역보조제로써의 활용에 개발 가능성이 있다는 것을 보여준다.

To evaluate the anti-tumor activity of Flammulina velutipes extract, we used an in vitro wound-healing assay, and an in vivo approach using a mouse melanoma model. Wound-healing activity in B16 cells was affected by the extract in a dose-dependent manner, indicating that the extract had anti-metastatic activity. The extract also exhibited strong anti-tumor activity against lung cancer when B16 cells were injected into mouse veins together with B16 melanoma cells. The results indicatethat the Flammulina velutipes extract decreased B16 cancer cell growth by inhibition of cell migration both in vitro and in vivo.

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and Interferon-γ (IFN-γ) production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased IFN-γ and TNF-α production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.