Page 107 - D. Cancer biology
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Ginsenoside Rh3 and three minor ginsenosides inhibits epithelial








                                                                                             mesenchymal transition (EMT) in neuroblastoma cells













                                                                                                                                                                                Jung-Mi Oh , Sun Young Park , and Sungkun Chun                                                                                                                                                              1,2
                                                                                                                                                                                                                                                                                                       1,2
                                                                                                                                                                                                                              1,2












                                                                                                                         1 Department of Physiology, Jeonbuk National University Medical School, Jeonju,  Korea




                                                                                                                  2  Brain Korea 21 Plus Program, Jeonbuk National University Medical School, Jeonju, Korea












          Ginseng has already been proved to exert potential benefits on antitumor activity via its antioxidant properties from other cancer cell lines. In this study, we



        investigated the potential pharmacological activity of several ginsenosides in neuroblastoma cell lines. Among all tested ginsenoside compounds, four minor



        ginsenosides had strong cytotoxicity and became more effective agents to display the protective effects. As a result, these compounds were significantly increased




        the apoptosis rate in dose dependent manner which was dependent by caspase activation. Also, we found that inhibition of the migration through scratch wound



        healing assay and invasion by treatment of minor ginsenosides. These results suggest that four minor ginsenosides might be promising compounds to have



        therapeutic effect on neuroblastoma cell lines.










                                                             Introduction                                                                                                3. Chemical structure of the Rh3, Rh2, CK and RK-1                                                                                                                                  6. Effects of caspase inhibitors on ginsenosides treated



                                                                                                                                                                                                                                                                                                                                                                                                            neuroblastoma cells


       •        Neuroblastoma (NB)is type of cancer that develops                                                                                                                      a                                                                           b



                during the early stage of an embryo or fetus and                                                                                                                                                                                                                                                                                           a                                                                             b



                originates in immature neuronal cells.







       •        Most of cases of NB occur in infancy and in children                                                                                                                                                                           Rh3                                                                          RK-1



                younger than 10 years old ages.

                                                                                                                                                                                       c                                                                            d





       •        Neuroblastoma is prevalent cancer type diagnosed in



                infant younger than 1 year old of ages.







       •        Ginsenosides are the major active ingredients of                                                                                                                                                                                Rh2                                                                              CK




                ginseng.








       •        Ginsenosides are divided into two types,                                                                                                                 4. Cytoprotective effect of ginsenosides in SK-N-BE(2) cells



                protopanaxatriol (PPT) and protopanaxadiol( PPD).                                                                                                              a                                                                            b                                                                                              7. Effects of caspase inhibitors on ginsenosides treated


                                                                                                                                                                                                                                                                                                                                                                                                         neuroblastoma cells


                                                                                                                                                                                                                                                                       120
                                                                                                                                                                                                                                                                                                                                 Rh3                         a
                                                                                                                                                                                                                                                                                                                                 Rh2
                                                                                                                                                                                                                                                                    Cell viability (%) 100
                                                                                                                                                                                                                                                                                                                                 CK

                                                                                                                                                                                                                                                                        80

                                                                                                                                                                                                                                                                        60
                                             Objectives & methods                                                                                                                                                                                                       40





       • What is the molecular mechanisms of  major and minor                                                                                                                                                                                                           20

                                                                                                                                                                                                                                                                          0
              ginsenoside effects on neuroblastoma  cells?                                                                                                                                                                                                                          0       2        4       6       8      10
                                                                                                                                                                                                                                                                                           Concentration (uM)


                                                                                                                                                                                                                                                                       120                                                  Rk-1
                      Cell growth rate : MTT
                                                                                                                                                                                                                                                                     Cell viability (%) 100
                                     assay                                                                                                                                                                                                                               80



                                                                                                                                                                                                                                                                         60

                                                                                                                                                                                                                                                                         40

                                                                                                                                                                                                                                                                         20

                                                                                                                                                                                                                                                                           0
                                                                                                                                                                                                                                                                                   0        2        5      10      15      20
                                                                                                                                                                                                                                                                                           Concentration (uM)                                                b






                                                                                                                                                                           5. Induction of apoptosis of SK-N-BE(2) cells by four minor



                                                                                                                                                                                                                                           ginsenosides



                                                                                                                                                                            a



















                                                                      Results






          1. Protopanaxatriol (PPT) and Protopanaxadiol( PPD)                                                                                                                                                                                                                                                                                                c

































                                                                                                                                                                            b






           2. Effect of various ginsenosides on viability of human


                                                        neuroblastoma cells


            a                                                                        b                                                                                                                                                                                                                                                                       d





















































                                                                                                                                                      Conclusions                                                                                                                                                                                                                                                    References






            ▪ Minor ginsenosides has better inhibition of proliferation of cells than major ginsenosides.                                                                                                                                                                                                                                              1. Andre N et al., Arch Pediatr 16:1158-1165 (2009)





           ▪ Four ginsenosides (RK-1, Rh2, Rh3 and CK) induce apoptosis of a concentration-dependent manner in neuroblastoma cells.                                                                                                                                                                                                                    2. Lei chen et al., Cell death and disease (2016)





           ▪ Four ginsenosides inhibits migration and invasion of human neuroblastoma cell line SK-N-BE(2).                                                                                                                                                                                                                                            3. Brodeur G.M. Nature Rev. Cancer 3, 203-216 (2003).
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