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      • Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells

        Putri, Herwandhani,Jenie, Riris Istighfari,Handayani, Sri,Kastian, Ria Fajarwati,Meiyanto, Edy Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

        A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV-0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with $IC_{50}$ values of $94.9{\mu}M$ and $49.0{\pm}0.2{\mu}M$, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.

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        Caesalpinia sappan L. heartwood ethanolic extract exerts genotoxic inhibitory and cytotoxic effects

        Edy Meiyanto,Beni Lestari,Raisatun Nisa Sugiyanto,Riris Istighfari Jenie,Rohmad Yudi Utomo,Ediati Sasmito,Retno Murwanti 경희대학교 융합한의과학연구소 2019 Oriental Pharmacy and Experimental Medicine Vol.19 No.1

        Brazilin and brazilein, the major compounds of Caesalpinia sappan L. (CS) have been reported to possess antioxidant and cytotoxic activities and could potentially be used as an antigenotoxic as well as an anticancer. This study was conducted to investigate the cytotoxic and antigenotoxic effects of CS ethanolic extract (CEE). In vivo mammalian micronucleus test of CEE at the dose of 500 mg/kg BW and 1000 mg/kg BW decreased the number of MNPCE and increased the ratio of PCE to NCE meaning that CEE performed antigenotoxic effect in an in vivo model. In contrast, CEE and doxorubicin (DOXO) performed cytotoxic effect on CHO-K1 cells under MTT assay with IC50 values of 67 μg/mL and 6 μM, respectively. Interestingly, treatment of CEE in combination with DOXO and H2O2 as genotoxic inducer decreased intracellular ROS levels. In addition, in vitro genotoxicity study by using cytokinesis-block micronucleus (CBMN) assay, both of Giemsa staining and flow cytometric analysis showed that the treatment of CEE increased the number of micronuclei and correlated with apoptotic induction results. Moreover, the combination of CEE and DOXO induced cells accumulation in Sub-G1 and G2/M phase. In conclusion, CEE performed antigenotoxic effect in an in vivo model and cytotoxic effect on CHO-K1 cells.

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