Potential Anticancer Effect of Bioactive Extract of Monk Fruit (<i>Siraitia grosvenori</i>) on Human Prostate and Bladder Cancer Cells — Oak Academic Publishing
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Potential Anticancer Effect of Bioactive Extract of Monk Fruit (<i>Siraitia grosvenori</i>) on Human Prostate and Bladder Cancer Cells
Department of Urology, New York Medical College, Valhalla, USA
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Department of Urology, New York Medical College, Valhalla, USA
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Department of Urology, New York Medical College, Valhalla, USA
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Department of Urology, New York Medical College, Valhalla, USA
1 Department of Urology, New York Medical College, Valhalla, USA
2 Department of Urology, New York Medical College, Valhalla, USA
3 Department of Urology, New York Medical College, Valhalla, USA
4 Department of Urology, New York Medical College, Valhalla, USA
Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides , with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto ò (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G 1 cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs w as also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.
Siegel, R.L., Miller, K.D., Wagle, N.S. and Jemal, A. (2023) Cancer Statistics, 2023. CA, 73, 17-48. https://doi.org/10.3322/caac.21763
Teo, M.Y., Rathkopf, D.E. and Kantoff, P. (2019) Treatment of Advanced Prostate Cancer. Annual Review of Medicine, 70, 479-499. https://doi.org/10.1146/annurev-med-051517-011947
Hirst, C.J., Cabrera, C. and Kirby, M. (2012) Epidemiology of Castration Resistant Prostate Cancer: A Longitudinal Analysis Using a UK Primary Care Database. Cancer Epidemiology, 36, e349-e353. https://doi.org/10.1016/j.canep.2012.07.012
Mansinho, A., Macedo, D., Fernandes, I. and Costa, L. (2018) Castration-Resistant Prostate Cancer: Mechanisms, Targets and Treatment. In: Schatten, H., Eds., Molecular & Diagnostic Imaging in Prostate Cancer, Advances in Experimental Medicine and Biology, Vol. 1126, Springer, Cham, 117-133. https://doi.org/10.1007/978-3-319-99286-0_7
Bilusic, M., Madan, R.A. and Gulley, J.L. (2017) Immunotherapy of Prostate Cancer: Facts and Hopes. Clinical Cancer Research, 23, 6764-6770. https://doi.org/10.1158/1078-0432.CCR-17-0019
Pow-Sang, J.M. and Seigne, J.D. (2000) Contemporary Management of Superficial Bladder Cancer. Cancer Control, 7, 335-339. https://doi.org/10.1177/107327480000700402
Kaufman, D.S., Shipley, W.U. and Feldman, A.S. (2009) Bladder Cancer. The Lancet, 374, 239-249. https://doi.org/10.1016/S0140-6736(09)60491-8
Shen, Z., Shen, T., Wientjes, M.G., et al. (2008) Intravesical Treatments of Bladder Cancer: Review. Pharmaceutical Research, 25, 1500-1510. https://doi.org/10.1007/s11095-008-9566-7
Malmstrom, P.U. (2003) Intravesical Therapy of Superficial Bladder Cancer. Critical Reviews in Oncology/Hematology, 47, 109-126. https://doi.org/10.1016/S1040-8428(03)00075-1
Cai, Y.Z., Luo, Q., Sun, M. and Corke, H. (2004) Antioxidant Activity and Phenolic Compounds of 112 Traditional Chinese Medicinal Plants Associated with Anticancer. Life Sciences, 74, 2157-2184. https://doi.org/10.1016/j.lfs.2003.09.047
Li, Y., Zhang, J.J., Xu, D.P., et al. (2016) Bioactivities and Health Benefits of Wild Fruits. International Journal of Molecular Sciences, 17, 1258-1285. https://doi.org/10.3390/ijms17081258
Zhang, J.J., Li, Y., Zhou, T., et al. (2016) Bioactivities and Health Benefits of Mushrooms Mainly from China. Molecules, 21, 938-954. https://doi.org/10.3390/molecules21070938
Pratheeshkumar, P., Sreekala, C., Zhang, Z., et al. (2012) Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets. Anti-Cancer Agents in Medicinal Chemistry, 12, 1159-1184. https://doi.org/10.2174/187152012803833035
Li, C., Lin, L.M., Sui, F., et al. (2014) Chemistry and Pharmacology of Siraitia grosvenorii: A Review. Chinese Journal of Natural Medicines, 12, 89-102. https://doi.org/10.1016/S1875-5364(14)60015-7
Dharmananda, S. (2004) Luo Han Guo, Sweet Fruit Used as Sugar Substitute and Medicinal Herb. https://www.itmonline.org/arts/luohanguo.htm
Zhou, Y., Zheng, Y., Ebersole, J. and Huang, C.F. (2009) Insulin Secretion Stimulating Effects of Mogroside V and Fruit Extract of Luo Han Kuo (Siraitia grosvenori Swingle). Acta Pharmaceutica Sinica, 44, 1252-1257.
Liu, C., Dai, L., Liu, Y., Dou, D., Sun, Y. and Ma, L. (2018) Pharmacological Activities of Mogrosides. Future Medicinal Chemistry, 10, 845-850. https://doi.org/10.4155/fmc-2017-0255
Liu, C., Dai, L., Liu, Y., et al. (2016) Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer. Nutrients, 8, 360-371. https://doi.org/10.3390/nu8060360
Takasaki, M., Konoshima, T., Murata, Y., et al. (2003) Anticarcinogenic Activity of Natural Sweeteners, Cucurbitane Glycosides, from Momordica grosvenori. Cancer Letters, 198, 37-42. https://doi.org/10.1016/S0304-3835(03)00285-4
Xu, Q., Chen, S.Y., Deng, L.D., Feng, L.P., Huang, L.Z. and Yu, R.R. (2013) Antioxidant Effect of Mogrosides against Oxidative Stress Induced by Palmitic Acid in Mouse Insulinoma NIT-1 Cells. Brazilian Journal of Medical & Biological Research, 46, 949-955. https://doi.org/10.1590/1414-431X20133163
Suzuki, Y.A., Tomoda, M., Murata, Y., Inui, H. and Sugiura, M. (2007) Antidiabetic Effect of Long-Term Supplementation with Siraitia grosvenori on the Spontaneously Diabetic Goto-Kakizaki Rat. British Journal of Nutrition, 97, 770-775. https://doi.org/10.1017/S0007114507381300
Di, R., Huang, M.T. and Ho, C.T. (2011) Anti-Inflammatory Activities of Mogrosides from Momordica grosvenori in Murine Macrophages and a Murine Ear Edema Model. Journal of Agricultural and Food Chemistry, 59, 7474-7481. https://doi.org/10.1021/jf201207m
Chiu, C.H., Wang, R., Lee, C.C., Lo, Y.C. and Lu, T.J. (2013) Biotransformation of Mogrosides from Siraitia grosvenorii Swingle by Saccharomyces cerevisiae. Journal of Agricultural and Food Chemistry, 61, 7127-7134. https://doi.org/10.1021/jf402058p
Goranov, A.I., Cook, M., Ricicova, M., et al. (2009) The Rate of Cell Growth Is Governed by Cell Cycle Stage. Genes & Development, 23, 1408-1422. https://doi.org/10.1101/gad.1777309
Sherr, C.J. (2000) The Pezcoller Lecture: Cancer Cell Cycles Revised. Cancer Research, 60, 3689-3695.
Brewer, J.W. and Diehl, J.A. (2000) PERK Mediates Cell-Cycle Exit during the Mammalian Unfolded Protein Response. PNAS, 97, 12625-12630. https://doi.org/10.1073/pnas.220247197
Mandl, J., Meszaros, T., Banhegyi, G. and Csala, M. (2013) Minireview: Endoplasmic Reticulum Stress: Control in Protein, Lipid, and Signal Homeostasis. Molecular Endocrinology, 27, 384-393. https://doi.org/10.1210/me.2012-1317
Lin, R., Hu, X., Chen, S., Shi, Q. and Chen, H. (2020) Naringin Induces Endoplasmic Reticulum Stress-Mediated Apoptosis, Inhibits β-Catenin Pathway and Arrests Cell Cycle in Cervical Cancer Cells. Acta Biochimica Polonica, 67, 181-188.
Singh, S.K., Banerjee, S., Acosta, E.P., Lillard, J.W. and Singh, R. (2017) Resveratrol induces Cell Cycle Arrest and Apoptosis with Docetaxel in Prostate Cancer Cells via a p53/p21WAF1/CIP1 and p27KIP1 Pathway. Oncotarget, 8, 17216-17228. https://doi.org/10.18632/oncotarget.15303
Yip, K.W. and Reed, J.C. (2008) Bcl-2 Family Proteins and Cancer. Oncogene, 27, 6398-6406. https://doi.org/10.1038/onc.2008.307