Recently, more and more researchers are investigating the effectiveness of using traditional Chinese medicine as a treatment to treat cancer. This work investigates the Cucurbitacin D, an active component found in the traditional Chinese medicine Trichosanthes kirilowii tuber. Its abilities to inhibit NF-κB activation and to induce apoptosis are studied. This work also examines the potential ability of Cucurbitacin D to inhibit TNF-induced NF-κB activation, to inhibit TNF-dependent IκBα degradation and TNF-dependent IκBα phosphorylation, to repress the TNF-induced NF-κB-dependent reporter gene expression, to potentiate the apoptosis effect, to down regulates the expression of anti-apoptotic proteins regulated by the NF-κB pathway, and to inhibits the expression of gene products involved in cell proliferation using methods such as the EMSA, western blotting, NF-κB-dependent reporter gene expression assay, TUNEL assay, live and dead assay, and the MTT assay. There are several possible results that can be derived from each testing. In this work, the final conclusion is that Cucurbitacin D could have the potential ability to inhibit NF-kB activation and therefore to induce apoptosis, so it could have the potential ability to reduce cancer cell progression.

Siyu Yang. Cucurbitacin D Inhibits NF-κB Activation, Thereby Inducing Apoptosis and Suppressing Tumor Growth. The Frontiers of Society, Science and Technology (2021) Vol. 3, Issue 2: 1-10. https://doi.org/10.25236/FSST.2021.030201.

[1] Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57-70. doi:10.1016/s0092-8674(00)81683-9

[2] Fesik, S. W. (2005). Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer, 5(11), 876-885. doi:10.1038/nrc1736

[3] Fulda, S. (2009). Apoptosis pathways and their therapeutic exploitation in pancreatic cancer. J Cell Mol Med, 13(7), 1221-1227. doi:10.1111/j.1582-4934.2009.00748.

[4] Attardi, L. D., & Jacks, T. (1999). The role of p53 in tumour suppression: lessons from mouse models. Cell Mol Life Sci, 55(1), 48-63.

[5] Yin, C., Knudson, C. M., Korsmeyer, S. J., & Van Dyke, T. (1997). Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature, 385(6617), 637-640.

[6] Ramachandran, I., Thavathiru, E., Ramalingam, S., Natarajan, G., Mills, W. K., Benbrook, D. M., Queimado, L. (2012). Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo. Oncogene, 31(22), 2725-2737.

[7] Leahy, K. M., Ornberg, R. L., Wang, Y., Zweifel, B. S., Koki, A. T., & Masferrer, J. L. (2002). Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res, 62(3), 625-631. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11830509

[8] Efferth, T., & Oesch, F. (2004). Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines. Biochem Pharmacol, 68(1), 3-10.

[9] Efferth, T., Giaisi, M., Merling, A., Krammer, P. H., & Li-Weber, M. (2007). Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One, 2(8), e693.

[10] Liu, Z., Liu, Q., Xu, B., Wu, J., Guo, C., Zhu, F., Shao, C. (2009). Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage. Mutat Res, 662(1-2), 75-83.

[11] Baumann, S., Fas, S. C., Giaisi, M., Muller, W. W., Merling, A., Gulow, K., Li-Weber, M. (2008). Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca2+-dependent apoptosis. Blood, 111(4), 2354-2363.

[12] Bensky, D., Clavey, S., Stöger, E. Gamble A (2004). Chinese Herbal Medicine Materia Medica, Seattle: Eastland Press. pp. 108–111. ISBN 0-939616-42-4. 

[13] Chan, S. H., Hung, F. S., Chan, D. S., & Shaw, P. C. (2001). Trichosanthin interacts with acidic ribosomal proteins P0 and P1 and mitotic checkpoint protein MAD2B. Eur J Biochem, 268(7), 2107-2112. doi:10.1046/j.1432-1327.2001.02091.

[14] Wang, P., & Li, J. C. (2007). Trichosanthin-induced specific changes of cytoskeleton configuration were associated with the decreased expression level of actin and tubulin genes in apoptotic Hela cells. Life Sci, 81(14), 1130-1140.

[15] Cai, Y., Xiong, S., Zheng, Y., Luo, F., Jiang, P., & Chu, Y. (2011). Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM. Cell Mol Immunol, 8(4), 359-367.

[16] Kim, S. R., Seo, H. S., Choi, H. S., Cho, S. G., Kim, Y. K., Hong, E. H., Ko, S. G. (2013). Trichosanthes kirilowii Ethanol Extract and Cucurbitacin D Inhibit Cell Growth and Induce Apoptosis through Inhibition of STAT3 Activity in Breast Cancer Cells. Evid Based Complement Alternat Med, 2013, 975350.

[17] Thoennissen, N. H., Iwanski, G. B., Doan, N. B., Okamoto, R., Lin, P., Abbassi, S., Koeffler, H. P. (2009). Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Res, 69(14), 5876-5884.

[18] Zhang, M., Sun, C., Shan, X., Yang, X., Li-Ling, J., & Deng, Y. (2010). Inhibition of pancreatic cancer cell growth by cucurbitacin B through modulation of signal transducer and activator of transcription 3 signaling. Pancreas, 39(6), 923-929.

[19] Aggarwal, B. B., Takada, Y., Shishodia, S., Gutierrez, A. M., Oommen, O. V., Ichikawa, H., Kumar, A. (2004). Nuclear transcription factor NF-kappa B: role in biology and medicine. Indian J Exp Biol, 42(4), 341-353. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15088683

[20] Shishodia, S., & Aggarwal, B. B. (2002). Nuclear factor-kappaB activation: a question of life or death. J Biochem Mol Biol, 35(1), 28-40.

[21] Sethi, G., Ahn, K. S., Pandey, M. K., & Aggarwal, B. B. (2007). Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood, 109(7), 2727-2735.

[22] Sung, B., Park, B., Yadav, V. R., & Aggarwal, B. B. (2010). Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors. J Biol Chem, 285(15), 11498-11507.

[23] Ahn, K. S., & Aggarwal, B. B. (2005). Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci, 1056, 218-233.

[24] Comsa, S., Ciuculescu, F., & Raica, M. (2012). Mesenchymal stem cell-tumor cell cooperation in breast cancer vasculogenesis. Mol Med Rep, 5(5), 1175-1180.

[25] Baldin, V., Lukas, J., Marcote, M. J., Pagano, M., & Draetta, G. (1993). Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev, 7(5), 812-821.

[26] Romano, M., & Claria, J. (2003). Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J, 17(14), 1986-1995.