Kajian Heat Shock Protein 90 (HSP90) Dalam Pencarian Kandidat Penghambatnya Melalui Ekplorasi Bahan Alam Indonesia: Review on Heat Shock Protein 90 (HSP90) for Exploration of Its Inhibitor Candidates Through Indonesian Natural Resources

Exploration on anticancer candidates on inhibition of Heat Shock Protein (HSP) activity are increasing in the past ten years. Some of HSP90 inhibitor candidates were in third phase of clinical trials. However, this issue is not followed by the emergency of HSP90 inhibitor research in Indonesia, not only study on natural source but also on synthetic candidates. This study aims to look the development of tracking HSP90 inhibitor candidates globally so that it can initiate the related research in Indonesia. Study of HSP90 and its inhibitors were taken from scientific articles in the range from 2009 to 2018. HSP90 and its inhibitors have important values in the dynamics of functions and stability of proteins to maintain survival of cells. This also include the oncogene proteins that involve in cell proliferation such as tyrosine kinases, transcription factors, and regulatory proteins that expression and interaction depend on HSP90. Expression of the transcription factor p53, Alk gene, Wnt gene, glucocorticoid receptors have also links with HSP90 protein activity. Some candidates for inhibitor of HSP90 have been entering clinical trials such as geldanamycin analogues, resorcinol derivatives, and purines analog. Candidates from natural sources that are also being developed such as luteolin, licochalcone A, oleochantal, novobiocin, epigallocathecin gallat, silybin, deguelin, and celastrol from terpenoid class, Apigenin from flavon class, Curcumin, and  Gambogat Acid. HSP90 inhibitors which are entering the third phase of clinical trial are ganetespib from the resorcinol derivative and retaspimycin from geldanamisin analog group. Exploration of HSP90 inhibitors from Indonesia natural resources still have great potential to be developed because they have high impact values as anticancer candidates

MOLECULAR ANALYSIS OF GENE EXPRESSION RELATED TO THE EFFECTS OF DLBS3233 TREATMENT IN DIFFERENTIATION OF 3T3-L1 PRE-ADIPOCYTE

Objective: DLBS3233 is a standardized extract combination containing Lagerstroemia speciosa and Cinnamomum burmannii. The effect of DLBS3233 on adipocyte differentiation was examined in this study.Methods: 3T3-L1 pre-adipocyte was used to investigate gene expression using the real-time reverse transcription polymerase chain reaction (RT-PCR) method. Oil red-O staining for detecting lipid formation was also carried out in this experiment.Results: DLBS3233 caused cell differentiation of 3T3-L1 pre-adipocytes into adipocytes which were indicated by positive results on staining cells with oil red-O on day 6 of the differentiation process. Analysis of gene expressions associated with adipogenesis (C/EBP-α, PPAR-γ, C/EBP-δ, FASn and adiponectin) showed an increase compared to control. In this study, DLBS3233 at a concentration of 5 μg/ml exhibited better differentiation effect than DLBS3233 at a concentration of 10 μg/ml.Conclusion: DLBS3233 can stimulate differentiation of 3T3-L1 pre-adipocytes into adipocytes.Keywords: DLBS3233, Adipogenesis, Gene expression analysis, Real-time RT-PC