Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Effect of Various Nutraceuticals on Oncoprotein Heparan Sulfatase-2 Activity in Breast Cancer Cell Line


Affiliations
1 Department of Biochemistry, CSIR-Central Food Technological Research Institute, K.R.S. Road, Mysuru-570 020, India
     

   Subscribe/Renew Journal


One in ten of all new cancers diagnosed worldwide are the cases of breast cancer and it is a most common form of cancer in women in both developing and developed countries. It is also the principal cause of death from cancer among women globally. Nutraceuticals, basically plant derived components are being used for the prevention and treatment of many diseases, including cancer. Heparan sulfatase-2 (hsulf-2) is a newly isolated oncoprotein, highly expressed in MCF-7 breast cancer cell line and inactivation of this protein possibly may prevent/impede the progression of the cancer. Many nutraceuticals viz. turmeric, ginger, soya and bael fruit extract as a whole and pure components curcumin and zerumbone have been studied in this report. Barring zerumbone, these nutraceuticals significantly inhibited the oncoprotein heparan sulfatase-2 (hsulf-2) activities isolated from MCF-7 breast cancer cell line, with an IC50 value at micro molar levels, indicating that these could be potential anticancer components. Curcumin inhibited cell proliferation with an IC50 value of 37.5 μM, subsequently induced apoptosis of breast cancer cell line. In conclusion, the findings of the present study may provide a basis for further study of these nutraceuticals in the treatment of breast cancer.

Keywords

Heparan Sulfatase-2, Nutraceuticals, Curcumin, Ginger, Zerumbone, Bael Fruit, Soya and Enzyme Activity.
User
Notifications

  • GLOBOCAN; New Global Cancer Data: 2018, 12th September 2018.
  • Liu, R.H. Dietary bioactive compounds and their health implications. J. Fd. Sci., 2013, 78, 18-28.
  • Bordoloi, D., Roy, N.K., Monisha, J., Padmavathi, G. and Kunnumakkara, A.B. Multi-targeted agents in cancer cell chemosensitization: what we learnt from curcumin thus far. Anticancer Drug Discov., 2016, 11, 67-97.
  • Gupta, S.C., Patchva, S., Koh, W. and Aggarwal, B.B. Discovery of curcumin, a component of golden spice and its miraculous biological activities. Clin. Exp. Pharmacol. Physiol., 2012, 39, 283-299.
  • Prasad, S., Gupta, S.C., Tyagi, A.K. and Aggarwal, B.B. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol. Adv., 2014, 32, 1053-1064.
  • Aggarwal, B.B., Gupta, S.C. and Sung, B. Curcumin: an orally bio available blocker of TNF and other pro-inflammatory biomarkers. Br. J. Pharmacol., 2013, 169, 1672-1692.
  • Gupta, S.C., Kismali, G. and Aggarwal, B.B. Curcumin, a component of turmeric: from farm to pharmacy. Biofactors, 2013, 39, 2-13.
  • Prasad, S. and Tyagi, A.K. Ginger and its Constituents: Role in Prevention and treatment of Gastrointestinal Cancer. Gastroenterology Research and Practice, 2015, 11, Article ID 142979.
  • Cheng, T.O. Cardiovascular effects of Danshen. Int. J. Cardiol., 2007, 121, 9-22.
  • Wasser, S., Ho, J.M., Ang, H.K. and Tan, C.E. Salvia Miltiorrhiza reduces experimentally induced hepatic fibrosis in rats. J. Hepatolo., 1998, 29, 760-771.
  • Ahn, Y.M., Kim, S.K. and Lee, S.H. Renoprotective effect of Tanshinone II A an active component of Salvia miltiorrhiza on rats with chronic kidney disease. Phytother. Res., 2010, 24, 1886-1892.
  • Mansara, P., Mrunal, K., Rashmi, D., Amol, C., Kavita, S and Ruchika, K.G. Improved antioxidant status by omega-3 fatty acid supplementation in breast cancer patients undergoing chemotherapy: A case series. J. Med. Case Rep., 2015, 9, 1-6.
  • Nabavi, S.F., Bilotto, S., Russo, G.L., Orhan, I.E., Habtemariam, S., Daglia, M., Devi, K.P., Loizzo, M.R., Tundis, R. and Nabavi, S.M. Omega-3 polyunsaturated fatty acids and cancer: Lessons learned from clinical trials. Cancer Metastasis Rev., 2015, 34, 359-380.
  • Arakaki, A.K., Mezencev, R., Bowen, N.J., Huang, Y., McDonald, J.F. and Skolnick, J. Identification of metabolites with anticancer properties by computational metabolomics. Mol. Cancer, 2008, 7, 57.
  • Parolin, C., Calonghi, N., Presta, E., Boga, C., Caruana, P., Naldi, M., Andrisano, V., Masotti, L. and Sartor, G. Mechanism and stereo selectivity of HDAC I inhibition by (R)-9-hydroxystearic acid in colon cancer. Biochim. Biophys. Acta., 2012,1821, 1334-1340.
  • Ferhi, S., Sara, S., Sakina, Z., Sara, C., Angela, F., Daniele, S., Antonio, D., Margherita, M. and Guy, D. Total phenols from grape leaves counteract cell proliferation and modulate apoptosis-related gene expression in MCF-7 and HepG2 human cancer cell lines. Molecules, 2019, 24, 612-626.
  • Kalra, E.K. Nutraceutical-Definition and Introduction. AAPS Pharm. Sci., 2003, 5, 25.
  • Reddy, C.G., Prakash, S.S. and Diwakar, L. Stilbene heterocycles: Synthesis, antimicrobial, antioxidant and anticancer activities. J. Pharm. Innov., 2015, 3, 24-30.
  • Kuo, Y.F., Su, Y.Z. and Flavokawain, B. A novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic. Biol. Med., 2010, 49, 214-226.
  • Petric, C.R., Braicu, C., Raduly, L., Zanoaga, O., Dragos, N., Monroig, P., Dumitrascu, D. and Berindan-Neagoe, I. Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. Onco. Targets Ther., 2015, 8, 2053-2066.
  • Lai, J.P., Sandhu, D.S., Yu, C., Han, T., Moser, C.D., Jackson, K.K., Guerrero, R.B., Aderca, I., Isomoto, H., Garrity-Park, M.M., Zou, H., Abdirashid M. Shire, David M. Nagorney, Schuyler O. Sanderson, Alex A. Adjei, Ju-Seog Lee, Snorri S. Thorgeirsson and Lewis R. Roberts. Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatol., 2008, 47, 1211-1222.
  • Nawroth, R., VanZante, A., Cervantes, S., McManus, M., Hebrok, M. and Rosen, S.D. Extracellular sulfatases, elements of the want signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One, 2007, 25, e392.
  • Morimoto-Tomita, M., Uchimura, K., Bistrup, A., Lum, D.H., Egeblad, M., Boudreau, N., Werb, Z. and Rosen, S.D. Sulf-2, A proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer. Neoplasia, 2005, 7, 1001-1010.
  • Lemjabbar, A.H., VanZante, A., Singer, M.S., Xue, Q., Wang, Y.Q., Tsay, D., He, B., Jablons, D.M. and Rosen, S.D. Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. Oncogene, 2010, 29, 635-646.
  • Horiuchi, N., Nakagava, K., Sasaki, Y., Minato, K., Fujiwara, Y., Nezu, K., Ohe, N. and Saijo,N. In vitro antitumor activity of mitomycin C derivative (RM49) and a new anticancer antibiotic (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay. Cancer Chemother. Pharmacol., 1988, 22, 246-50.
  • Gherghi, I.C., Girousi, S.T., Voulgaropoulos, A. and Tzimou-Tsitouridou, R. Study of interactions between DNA-ethidium bromide (EB) and DNA-acridine orange (AO), in solution, using hanging mercury drop electrode (HMDE). Talanta, 2003, 61, 103-112.
  • Chenfang, Z., Liu, H., Xin, Z., Xin, N. and Yan, G. Sulfatase-2 promotes breast cancer progression through regulating some tumor related factors. Oncol. Rep., 2016, 35, 1318-1328.
  • Park, M.J., Kim, E.H., Park, I.C., Lee, H.C., Woo, S.H., Lee, J.Y., Hong, Y.J., Rhee, C.H., Choi, S.H., Shim, B.S., Lee, S.H. and Hong, S.I. Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up regulating cyclin dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int. J. Oncol., 2002, 21, 379 383.
  • Shan, H., Yingchun, X., Liwei, M., Liming, H. and He, S. Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Experiment. Therapeutic. Med., 2018, 16, 1266-1272.
  • Park, C., Kim, G.Y., Kim, G.D., Choi, B.T., Park,Y.M. and Choi, Y.H. Induction of G2/M arrest and inhibition of cyclooxygenase 2 activity by curcumin in human bladder cancer T24 cells. Oncol. Rep., 2006, 15, 1225 1231.
  • Eid, E.E.M., Abdulrahman, S.A., Sanaz, K., Alian, A.A., Faizul, A., Ismail, M.T., Habibullah, K., Mothannasadiq, A.Q. and Mohammed, A.A. Zerumbone induces apoptosis in breast cancer cells by targeting αvβ3 integrin upon co-administration with TP5-iRGD peptide. Molecules, 2019, 24, E2554.
  • Tao, L.V., Wenjing, Z. and Xiaoli, H. Zerumbone suppresses the potential of growth and metastasis in hepatoma Hep G2 cells via the MAPK signaling pathway. Oncol. Lett, 2018, 15, 7603-7610.
  • Junkyu, H., Yui, K., and Hiroko, I. Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation. Cytotechnol., 2013, 65, 973-978.
  • Agarwal, A., Preeti, V. and Goyal, P.K. Chemomodulatory effects of Aegle Marmelos against DMBA induced skin tumorigenesis in Swiss Albino mice. Asian Pacific J. Can. Prev., 2010, 11, 1311-1314.
  • Kausar, H., Bhasin, G., Zargar, M.A. and Athar, M. Palm oil alleviates 12-O-tetradecanoylphorbol13-acetate-induced tumor promotion response in murine skin. Cancer lett., 2003, 192, 151-160.

Abstract Views: 203

PDF Views: 1




  • Effect of Various Nutraceuticals on Oncoprotein Heparan Sulfatase-2 Activity in Breast Cancer Cell Line

Abstract Views: 203  |  PDF Views: 1

Authors

Hemakumar C.
Department of Biochemistry, CSIR-Central Food Technological Research Institute, K.R.S. Road, Mysuru-570 020, India
Shylaja M. Dharmesh
Department of Biochemistry, CSIR-Central Food Technological Research Institute, K.R.S. Road, Mysuru-570 020, India
Ravendra Pratap Singh
Department of Biochemistry, CSIR-Central Food Technological Research Institute, K.R.S. Road, Mysuru-570 020, India

Abstract


One in ten of all new cancers diagnosed worldwide are the cases of breast cancer and it is a most common form of cancer in women in both developing and developed countries. It is also the principal cause of death from cancer among women globally. Nutraceuticals, basically plant derived components are being used for the prevention and treatment of many diseases, including cancer. Heparan sulfatase-2 (hsulf-2) is a newly isolated oncoprotein, highly expressed in MCF-7 breast cancer cell line and inactivation of this protein possibly may prevent/impede the progression of the cancer. Many nutraceuticals viz. turmeric, ginger, soya and bael fruit extract as a whole and pure components curcumin and zerumbone have been studied in this report. Barring zerumbone, these nutraceuticals significantly inhibited the oncoprotein heparan sulfatase-2 (hsulf-2) activities isolated from MCF-7 breast cancer cell line, with an IC50 value at micro molar levels, indicating that these could be potential anticancer components. Curcumin inhibited cell proliferation with an IC50 value of 37.5 μM, subsequently induced apoptosis of breast cancer cell line. In conclusion, the findings of the present study may provide a basis for further study of these nutraceuticals in the treatment of breast cancer.

Keywords


Heparan Sulfatase-2, Nutraceuticals, Curcumin, Ginger, Zerumbone, Bael Fruit, Soya and Enzyme Activity.

References





DOI: https://doi.org/10.21048/ijnd.2020.57.2.24708