Purpose : This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Methods: Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 μM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-β1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-β1, TGF-β1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase–polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Results: Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P<0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P<0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P>0.05). In line with our findings, the expressions of TGF-β1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P<0.05) versus control. Conclusion: Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial–mesenchymal transition markers by activating TGF-β/Smad pathways.

ABSTRAK Masa remaja merupakan masa peralihan di mana terjadi pertumbuhan dan perkembangan yang  pesat  baik  secara  fisik,  psikologis  maupun  intelektual. Pada masa ini, remaja rentan mengalami masalah seksualitas atau kesehatan reproduksi terutama bagi remaja dengan pengetahuan yang kurang mengenai kesehatan reproduksi, keputihan, kanker payudara dan cara melakukan SADARI. SMAN 27 Jakarta Pusat merupakan sekolah yang memiliki proporsi siswi putri yang banyak dengan rentang usia yang tepat untuk melakukan pencegahan dini terhadap masalah kesehatan reproduksi remaja. Oleh karena itu perlu dilakukan kegiatan pengabdian masyarakat melalui penyuluhan untuk meningkatkan pengetahuan remaja putri mengenai kesehatan reproduksi remaja, keputihan, kanker payudara dan pelatihan SADARI. Materi diberikan secara daring melalui power point dan penanyangan video. Sebelum dan setelah dilakukan penyuluhan, peserta akan diminta untuk mengerjakan pertanyaan mengenai topik tersebut. Hasil pretest dan posttest ditampilkan dalam tabel deskriptif. Berdasarkan hasil analisis diketahui bahwa terdapat peningkatan pengetahuan remaja putri perihal penularan infeksi saluran reproduksi, penyebab keputihan, dampak keputihan, factor resiko kanker payudara, pencegahan kanker payudara, pemeriksaan deteksi kanker payudara dan waktu pemeriksaan SADARI. Sehingga dapat disimpulkan bahwa kegiatan pengabdian masyarakat ini telah berhasil meningkatkan pengetahuan mengenai kesehatan reproduksi remaja, keputihan dan kanker payudara pada pelajar putri SMAN 27 Jakarta Pusat. Kata Kunci: Keputihan, SADARI, Kesehatan Reproduksi Remaja  ABSTRACT Adolescence is a period of transition where there is rapid growth and development both physically, psychologically, and intellectually. At this time, adolescents are vulnerable to reproductive health problems, especially adolescents with less knowledge about reproductive health, vaginal discharge, breast cancer, and how to do Breast Self Examination (BSE). SMAN 27 Central Jakarta is a school with a large proportion of female students with a suitable age range for the early prevention of adolescent reproductive health problems. Therefore, it is necessary to carry out community service activities through counselling to increase young women's knowledge about adolescent reproductive health, vaginal discharge, breast cancer, and BSE training. Materials are given online through power points and video shows. Before and after the counselling, participants will be asked to work on questions about the topic. The results of the pretest and posttest are shown in a descriptive table. Based on the results of the analysis, it is known that there is an increase in the knowledge of young women regarding the transmission of reproductive tract infections, the causes of vaginal discharge, the impact of vaginal discharge, risk factors for breast cancer, breast cancer prevention, breast cancer detection examinations and BSE examination time. So, it can be concluded that this community service activity has increased knowledge about adolescent reproductive health, vaginal discharge, and breast cancer in female students of SMAN 27 Central Jakarta. Keywords: Vaginal Discharge, BSE, Adolescent Reproductive Health

Objective: Alpha-mangostin (α-MG) has been shown to possess antifibrotic effects. However, the specific mechanism of action of this compoundremains poorly understood. Therefore, the aim of this study was to investigate the effect of α-MG on the expression levels of transforming growthfactor (TGF)-β1 and matrix metalloproteinase-3 (MMP3) in hepatic stellate cells (HSCs) induced by TGF-β.Methods: Immortalized HSCs and LX-2 cells were incubated with TGF-β with or without α-MG (5 and 10 μM). The viability of LX-2 cells was assessedusing the Trypan Blue Exclusion Method. The effect of α-MG on cell morphology and the mRNA expression levels of TGF-β1, TGF-β receptor, and MMP3was then evaluated.Results: TGF-β enhanced the proliferation of HSCs and caused significant increases in the expression levels of TGF-β1, TGF-β receptor, and MMP3.α-MG treatment reduced the proliferation of HSCs and decreased the expression levels of TGF-β1, TGF-β1 receptor, and MMP3.Conclusion: α-MG is a potential antifibrotic agent due to its antiproliferative and antifibrogenic effects, mainly by suppressing the expression of TGF-βand MMP3 on the surfaces of activated HSCs.

Background: Sorafenib is the first-line systemic option for treatment in advanced liver cancer. However, sorafenib resistance may develop rapidly, which may involve apoptosis and oxidative stress dysregulations. Several alternative treatments have been suggested to alleviate the delayed resistance of cancer cells to sorafenib, including alpha mangostin (AM). According to an earlier study, AM might be able to overcome doxorubicin resistance in hepatocellular cancer cells. Objective: The aim of this study was to investigate the effects of AM in sorafenib-surviving HepG2 cells, a hepatocellular carcinoma (HCC) cell line. Methods: Sorafenib 10 µM was used to treat HepG2 to obtain sorafenib-surviving cells. Subsequently, sorafenib surviving cells were treated with DMSO -(vehicle) or sorafenib (SF) 10 µM or AM 20 µM, or SF 10 µM + AM 20 µM. Afterward, the cells were counted, collected and extracted for RNA. The mRNA expressions of Ki-67, c-Jun, Bcl-2, Bax, Caspase-3 and -9, GPx, and MnSOD were then quantified using qRT-PCR. Results: Treatment of alpha-mangostin, alone or in combination with sorafenib combined enhanced the expressions of proliferation markers, Ki-67 and c-Jun. In addition, there was a marked increase in mRNA expressions of Bax and BCl2, but not Caspase-3 and -9. There were amplifications of antioxidant markers expressions, GPx, and MnSOD after AM or a combination of sorafenib and AM. Conclusion: Treatment of alpha mangostin in sorafenib-surviving HCC cells caused an increase in proliferation markers, which might be explained by the reduced expressions of apoptosis markers and enhancement of antioxidant markers.