在台灣地區人類十大死因之中，惡性腫瘤始終高居第一位。因此，在一般被認為溫和的中草藥裡，尋找適合的癌症治療藥物，並希望能進一步探究其是否具備癌症預防的效果。在中草藥桑白皮中，經粗萃取而得化合物之一，Morusin，發現對於腫瘤細胞的生長有抑制的情形，在先前的研究已知Morusin可以抑制大腸直腸癌細胞HT-29，主要是透過粒線體膜電位喪失，並且使得Caspase 活性增加，產生細胞凋亡的情形。經由MTT assay證實，morusin也可造成肝癌細胞Hep 3B細胞凋亡，其六天的IC50為7.14uM，在其他癌症細胞也會有抑制情形。更深入探討morusin造成癌症細胞產生apoptosis的其他因子。首先，在與癌症有密切關係的轉錄因子，NF-kB方面，發現NF-kB入核的情形被morusin抑制，在功能方面也發現，NF-kB與DNA結合的能力也被morusin抑制，在此可以推測morusin主要是藉由降低轉錄因子NF-kB的表現，而使得原本不斷生長的癌症細胞，其增生能力受到抑制。而NF-kB路徑上游的受許多因子調控，在與細胞增生與生存相關的路徑，Akt路徑，發現在這條路徑上的相關的調控分子，也受到影響。因此可以證明morusin對癌症細胞的影響，主要是令其與增生相關PI3K-Akt路徑受到抑制，而使NF-kB下游調控許多與生存相關的基因與蛋白質也受到抑制。另外，在Hep 3B細胞中，也發現，morusin誘使其產生細胞凋亡情形；在細胞週期的分析中，發現sub-G1期DNA量增加，與apoptotic body產生，主要是經由caspase 9的表現量增加，使得caspase activated DNase(DFF40)在細胞核裡表現量增加，進而切割細胞的DNA。所以，本研究中證實morusin對大腸直腸癌細胞造成抑制情形，是經由Akt，而在肝癌細胞中也可誘發其細胞凋亡的產生，藉由本實驗可以發現morusin作為癌症治療藥物的潛力，並希望在將來能夠更進一步研究其預防癌症的能力與在臨床上應用的可能。

　Colorectal and hepatocellular carcinoma cause leading malignant death worldwide. Since the ways to treat cancer are still limited, Chinese herbal medicine became a choice to expand. The crude extracts of M. australis (Moraceae) are remedy used to treat disease in Taiwan. The specific goal of the present study is to determine the anti-tumor mechanism of morusin, isolated from M. australis, in human colorectal and hepatocellular carcinoma cell lines. Previous experimental results revealed that morusin inhibited the growth of human colorectal cancer HT-29 cells by the activation of caspases and loss of mitochondria membrane potential. The present study further demonstrated that NF-kB and its DNA biding activity were decreased after morusin treatment in HT-29 cells. Decrease in phosphorylation of PDK1, Akt, IKK, IkBandBad, the upstream regulators of NF-kB, was also observed. In hepatocellular carcinoma Hep 3B cells, increase of sub-G1 and nuclear condensation were induced by morusin. The IC50 of morusin in Hep 3B cells was 7.1uM which is far lower than 29.8uM in peripheral blood mononuclear cells (PBMC). Activation of caspase 9, decrease in DFF-45, increase of nuclear DFF-40, and suppression in NF-kB level and its DNA biding activity were also observed in Hep 3B cells. These findings suggest that morusin induce apoptosis of cancer cells through the inhibition of NF-kB by downregulation of Akt signaling pathway. The apoptotic mechanism induced by morusin provide a new field in cancer therapy.

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李時珍.本草綱目.木部.桑.1596
趙健麟（民93）Morusin經由細胞凋亡抑制大腸直腸癌細胞生長之作用機轉。國立成功大學微生物及免疫學研究所論文。中華民國。台南