아스피린과 아스피린의 deacetylated form인 sodium salicylate (NaSal)은 대장암, 폐암 및 유방암을 비롯한 다양한 암의 항암제 활성을 나타내는 것으로 잘 알려져 있다. A549 폐암 세포주에 저농도의 NaSal과 genistein을 함께 복합 처리시 상승작용에 의해 세포사멸을 증가시켜서 NaSal에 의한 암억제 효과를 증대시킴을 이미 밝힌바 있다. 본 연구에서는 A549가 아닌 다른 암세포주와 in vitro solid tumor model인 multicellular spheroids (MTS)을 이용하여 NaSal과 genistein 복합처리 효과를 조사하였다. NaSal/genistein 복합 처리시 A549 세포주와 마찬가지로 HCT116 세포주에서도 세포사멸이 유도되었지만, MCF-7 세포주에서는 유도되지 않았다. 흥미롭게도, MCF-7 세포주는 MTS로 배양되는 동안 NaSal/genistein 복합 처리에 의해 세포 죽음을 나타내었다. 세포 죽음의 형태는 MCF-7 MTS의 발달 단계에 따라 세포사멸 또는 세포괴사로 나타났다. MCF-7 MTS에서의 세포사멸은 불완전한 양상을 보였다. 즉 염색체가 응축되고 쪼개지지만, 핵막은 여전히 관찰되었다. 이상의 연구 결과 NaSal/genistein 복합처리는 MCF-7 MTS 배양 system에서 불완전한 세포사멸과 세포괴사를 일으킴을 알 수 있었다.
아스피린과 아스피린의 deacetylated form인 sodium salicylate (NaSal)은 대장암, 폐암 및 유방암을 비롯한 다양한 암의 항암제 활성을 나타내는 것으로 잘 알려져 있다. A549 폐암 세포주에 저농도의 NaSal과 genistein을 함께 복합 처리시 상승작용에 의해 세포사멸을 증가시켜서 NaSal에 의한 암억제 효과를 증대시킴을 이미 밝힌바 있다. 본 연구에서는 A549가 아닌 다른 암세포주와 in vitro solid tumor model인 multicellular spheroids (MTS)을 이용하여 NaSal과 genistein 복합처리 효과를 조사하였다. NaSal/genistein 복합 처리시 A549 세포주와 마찬가지로 HCT116 세포주에서도 세포사멸이 유도되었지만, MCF-7 세포주에서는 유도되지 않았다. 흥미롭게도, MCF-7 세포주는 MTS로 배양되는 동안 NaSal/genistein 복합 처리에 의해 세포 죽음을 나타내었다. 세포 죽음의 형태는 MCF-7 MTS의 발달 단계에 따라 세포사멸 또는 세포괴사로 나타났다. MCF-7 MTS에서의 세포사멸은 불완전한 양상을 보였다. 즉 염색체가 응축되고 쪼개지지만, 핵막은 여전히 관찰되었다. 이상의 연구 결과 NaSal/genistein 복합처리는 MCF-7 MTS 배양 system에서 불완전한 세포사멸과 세포괴사를 일으킴을 알 수 있었다.
Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 ...
Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.
Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.
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문제 정의
In this study, we examined the effects of NaSal/genis-tein-combined treatment in 2D culture and MTS system. Here we show that the combined treatment induces apoptosis in HCT116 cells as well as A549 cells.
Previously, we observed a synergistic effect of combined treatment of NaSal and genistein to induce apoptosis in A549 lung cancer cells. In this study, we examined the effects of the combined treatment in other cancer cells. HO/PI double staining method was used to identify necrosis (a tumor-promoting cell death type) as well as apoptosis (a tumor-suppressive cell death type); HO penetrates non-selectively plasma membrane of both damaged and intact cells and binds to DNA, causing a blue nuclear fluorescence, while PI penetrates only cells with damaged-membranes, causing red nuclear fluorescence.
참고문헌 (25)
Amann, R. and Peskar, B. A. 2002. Anti-inflammatory effects of aspirin and sodium salicylate. Eur. J. Pharmacol. 447, 1-9.
Bellosillo, B., Pique, M., Barragan, M., Castano, E., Villamor, N., Colomer, D., Montserrat, E., Pons, G. and Gil, J. 1998. Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells. Blood 92, 1406-1414.
Dikshit, P., Chatterjee, M., Goswami, A., Mishra, A. and Jana, N. R. 2006. Aspirin induces apoptosis through the inhibition of proteasome function. J. Biol. Chem. 281, 29228-29235.
Flossmann, E. and Rothwell, P. M. 2007. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 369, 1603-1613.
Garg, A. K., Buchholz, T. A. and Aggarwal, B. B. 2005. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid. Redox Signal. 7, 1630-1647.
Horning, J. L., Sahoo, S. K., Vijayaraghavalu, S., Dimitrijevic, S., Vasir, J. K., Jain, T. K., Panda, A. K. and Labhasetwar, V. 2008. 3-D tumor model for in vitro evaluation of anticancer drugs. Mol. Pharm. 5, 849-862.
Jeong, E. K., Lee, S. Y., Jeon, H. M., Ju, M. K., Kim, C. H. and Kang, H. S. 2010. Role of extracellular signal-regulated kinase (ERK)1/2 in multicellular resistance to docetaxel in MCF-7 cells. Int. J. Oncol. 37, 655-661.
Kim, C. H., Jeon, H. M., Lee, S. Y., Ju, M. K., Moon, J. Y., Park, H. G., Yoo, M. A., Choi, B. T., Yook, J. I., Lim, S. C., Han, S. I. and Kang, H. S. 2011. Implication of snail in metabolic stress-induced necrosis. PLoS One 6, e18000.
Kim, C. H., Kim, M. Y., Moon, J. Y., Hwang, J. W., Lee, S. Y., Joo, Y. M., Han, S. I., Park, H. G. and Kang, H. S. 2008. Implication of NAG-1 in synergistic induction of apoptosis by combined treatment of sodium salicylate and PI3K/MEK1/2 inhibitors in A549 human lung adenocarcinoma cells. Biochem. Pharmacol. 75, 1751-1760.
Klampfer, L., Cammenga, J., Wisniewski, H. G. and Nimer, S. D. 1999. Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood 93, 2386-2394.
Law, B. K., Waltner-Law, M. E., Entingh, A. J., Chytil, A., Aakre, M. E., Norgaard, P. and Moses, H. L. 2000. Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J. Biol. Chem. 275, 38261-38267.
Lee, E. J., Park, H. G. and Kang, H. S. 2003. Sodium salicylate induces apoptosis in HCT116 colorectal cancer cells through activation of p38MAPK. Int. J. Oncol. 23, 503-508.
Lee, S. Y., Jeong, E. K., Jeon, H. M., Ju, M. K., Kim, C. H., Park, H. G. and Kang, H. S. 2011. HMGB1 Switches Alkylating DNA Damage-Induced Apoptosis to Necrosis. J. Life Sci. 21, 953-960.
Marra, D. E., Simoncini, T. and Liao, J. K. 2000. Inhibition of vascular smooth muscle cell proliferation by sodium salicylate mediated by upregulation of p21(Waf1) and p27(Kip1). Circulation 102, 2124-2130.
Ruchaud, S., Korfali, N., Villa, P., Kottke, T. J., Dingwall, C., Kaufmann, S. H. and Earnshaw, W. C. 2002. Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation. Embo J. 21, 1967-1977.
Tomes, L., Emberley, E., Niu, Y., Troup, S., Pastorek, J., Strange, K., Harris, A. and Watson, P. H. 2003. Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res. Treat. 81, 61-69.
Ulrich, C. M., Bigler, J. and Potter, J. D. 2006. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat. Rev. Cancer 6, 130-140.
Yeh, T. C., Chiang, P. C., Li, T. K., Hsu, J. L., Lin, C. J., Wang, S. W., Peng, C. Y. and Guh, J. H. 2007. Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult. Biochem. Pharmacol. 73, 782-792.
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