Chemopreventive Potentials of Saururus chinensison Human Osteosarcoma Cancer Stem Cells In vitro

Abstract

암발생과암전이를유발하는강력한이유때문에암줄기세포사멸에대한여러가지처리가요구된다. 그러므로, 암줄기세포를제거하기위한전략적접근은중요한의학적적용들이요구된다. 본연구의목적은동양의학에서많이사용되는삼백초의항암제로서의효과를검사하고, 골수암줄기세포의사멸에관여하는지에대한검증연구이다 암줄기세포의in vitro모델을이용하여본연구에서는 CAL-72 골수암세포에서 CD133+의암줄기세포집단이존재함을밝혀내었으며이세포에서특이적인사멸기작을나타내었다. 이줄기세포에서처리된삼백초추출물은암줄기세포특이사멸반응을보였으며, 놀랍게도, 정상적인중간엽줄기세포에서는사멸반응을보이지않았다. 유세포분석기를통한분석결과에서도삼백초처리구의암줄기세포는 G2/M 단계에서의사멸기작을보여주었다. 삼백초는또한줄기세포의자가증식를억제하는특성을보였으며, 암세포의전형적인형태인 spheroid 형성을억제하고암줄기세포의이동과전이억제에상당한영향을끼치고있음을확인할수있었다. 재미있게도, 삼백초의경우에세포사멸신호전달단계에서 NF-κB와 Akt 경로에의하여세포사멸에관여함을증명하였다. 결과적으로삼백초의경우골수암유래의줄기세포의사멸에지대한영향을끼침을알수있었다. 암발생의기전은매우복잡한과정이지만, 본연구에서처럼삼백초와같은천연물들이골수암의발생억제에매우유용할것으로사료된다.

The demand for the treatment of cancer stem cells (CSCs) has been on rise due to their strong potency to cause tumor initiation and progression. Therefore, the strategy to eradicate CSCs should have significant clinical implications. The objective of this study is to examine whether chemopreventive potentials of Saururus chinensis (SC),a perennial herb in the Oriental folk medicine, in inhibiting stem cell characteristics of osteosarcoma CSCs. Using in vitro models of osteosarcoma CSCs we demonstrated that human Cal-72 osteosarcoma cells contain a small population of CD133+ CSCs which are responsive to SC treatment. SC significantly inhibited the cell viability of osteosarcoma CSCs, whereas it had no inhibitory effect on human mesenchymal stromal/stem cells (hMSCs). FACS analysis showed that the increased concentration of SC concomitantly enhanced the apoptosis of osteosarcoma CSCs via G2/M arrest. SC also potentially restricted the self-renewal capacity, associated with reduced spheroid formation, and suppressed migration and invasion of osteosarcoma CSCs. Interestingly, SC inhibited the cell survival pathways, the Nuclear factor-κB (NF-κB) and Akt pathways. These data propose that SC can eliminate osteosarcoma CSC-characteristics. Since carcinogenesis is a complex process, herbal medicine like SC will be beneficial for the prevention and/or treatment of osteosarcoma.