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<!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Description>generated by an Adobe application</o:Description> <o:Version>11.5606</o:Version> </o:DocumentProperties> </xml><![endif]--> <p class="Abstrakbody"><em><span style="font-size: 9.0pt;">Hedyotis corymbosa</span></em><span style="font-size: 9.0pt;"> L. with ursolic acid as the main compound is one of the plants that has been used for traditional medicine including to cure breast cancer disease. The aim of this research is to examine the cytotoxic activity of rumput mutiara herb ethanolic extract (ERM) and its effect in combination with doxorubicin against MCF-7 breast cancer cell line as cell model of doxorubicin resistance. <em>Hedyotis corymbosa</em> L. herb powder extraction was done by maceration using ethanol 96% then the extract is detected for ursolic acid content. Cell viability assay of ERM, doxorubicin and<span style="mso-spacerun: yes;">&nbsp; </span>the combination of ERM and doxorubicin treatments were carried out by MTT assay to determine IC</span><span style="font-size: 5.0pt; position: relative; top: 2.5pt; mso-text-raise: -2.5pt;">50</span><span style="font-size: 9.0pt;"><span style="mso-spacerun: yes;">&nbsp;</span>and CI (Combination Index). Cell cycle distribution was determined by flowcytometry. Apoptosis assay was performed by ethidum bromide-acridine orange DNA staining method. Investigation on Bcl-2 expression was determined by immunocytochemistry method. Thin Layer Chromatography of ERM had similar Rf with ursolic acid standard: 0,6. ERM and doxorubicin inhibited cell growth against MCF-7 with IC</span><span style="font-size: 5.0pt; position: relative; top: 2.5pt; mso-text-raise: -2.5pt;">50</span><span style="font-size: 9.0pt;"><span style="mso-spacerun: yes;">&nbsp; </span>of 77 &micro;g/mL and 349 nM (0,19 &micro;g/mL) respectively. Combination of ERM and doxorubicin showed synergistic effect (CI 0.66-0.99). Combination of 25 &igrave;g/mL ERM- 200 nM doxorubicin induced apoptosis and decreased Bcl-2 expression but showed no cell accumulation on cell cycle. Doxorubicin induced high cell accumulation in G2/M phase, but ERM at the concentration of 25 &igrave;g/mL had a low effect in G1 phase, and ERM IC</span><span style="font-size: 5.0pt; position: relative; top: 2.5pt; mso-text-raise: -2.5pt;">50</span><span style="font-size: 9.0pt;"><span style="mso-spacerun: yes;">&nbsp;</span>did not induce cell accumulation otherwise apoptosis. These results concluded that the apoptosis mechanism of combination doxorubicin-ERM is mediated by cell cycle arrest and non cell cycle arrest. Therefore ERM has a potential activity to be developed as co-chemotherapeutic agent.</span></p> <p class="MsoNormal" style="text-align: justify; text-justify: inter-ideograph; mso-layout-grid-align: none; text-autospace: none;"><span style="font-size: 9.0pt; font-family: &quot;Book Antiqua&quot;; mso-fareast-font-family: &quot;MS Mincho&quot;; mso-bidi-font-family: &quot;Book Antiqua&quot;; color: black; mso-ansi-language: EN-GB; mso-fareast-language: JA;">&nbsp;</span></p> <!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:HyphenationZone>36</w:HyphenationZone> <w:PunctuationKerning /> <w:ValidateAgainstSchemas /> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:Compatibility> <w:BreakWrappedTables /> <w:SnapToGridInCell /> <w:WrapTextWithPunct /> <w:UseAsianBreakRules /> <w:DontGrowAutofit /> <w:UseFELayout /> </w:Compatibility> </w:WordDocument> </xml><![endif]--><!--[if gte mso 9]><xml> <w:LatentStyles DefLockedState="false" LatentStyleCount="156"> </w:LatentStyles> </xml><![endif]--><!--[if gte mso 10]> <mce:style><! /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} --> <!--[endif] -->