Garcinol extracted from Garcinia indica fruit peel and leaves is a polyisoprenylated benzophenone. In traditional medicine it was used for its antioxidant and anti-inflammatory properties. Several studies have shown anti-cancer properties of garcinol in cancer cell lines and experimental animal models. Garcinol action in cancer cells is based on its antioxidant and anti-inflammatory properties, but also on its potency to inhibit histone acetyltransferases (HATs). Recent studies indicate that garcinol may also deregulate expression of miRNAs involved in tumour development and progression. This paper focuses on the latest research concerning garcinol as a HAT inhibitor and miRNA deregulator in the development and progression of various cancers. Garcinol may be considered as a candidate for next generation epigenetic drugs, but further studies are needed to establish the precise toxicity, dosages, routes of administration, and safety for patients.

Rhabdomyosarcoma (RMS) is a malignant soft tissue cancer that develops mostly in children and young adults. With regard to histopathology, four rhabdomyosarcoma types are distinguishable: embryonal, alveolar, pleomorphic and spindle/sclerosing. Currently, increased amounts of evidence indicate that not only gene mutations, but also epigenetic modifications may be involved in the development of RMS. Epigenomic changes regulate the chromatin architecture and affect the interaction between DNA strands, histones and chromatin binding proteins, thus, are able to control gene expression. The main aim of the study was to assess the role of protein arginine methyltransferases (PRMT) in the cellular biology of rhabdomyosarcoma. In the study we used two pan-inhibitors of PRMT, called AMI-1 and SAH, and evaluated their effects on proliferation and apoptosis of RMS cells. We observed that AMI-1 and SAH reduce the invasive phenotype of rhabdomyosarcoma cells by decreasing their proliferation rate, cell viability and ability to form cell colonies. In addition, microarray analysis revealed that these inhibitors attenuate the activity of the PI3K-Akt signaling pathway and affect expression of genes related to it.

Rhabdomyosarcoma (RMS) is a malignant tumour of the soft tissues. There are two main histopathological types: alveolar and embryonal. RMS occurs mainly in childhood and is a result of the deregulation of growth and differentiation of muscle cell precursors. There is an increasing amount of data indicating that numerous epigenetic alterations within chromatin and histone proteins are involved in the pathogenesis of this malignancy. Histone acetylation is one of the most important epigenetic modifications that is catalysed by enzymes from the group of histone acetyltransferases (HAT). In this study, the impact of the natural histone acetyltransferase inhibitors (HATi)—garcinol (GAR) and anacardic acid (AA)—on the biology of RMS cells was evaluated through a series of in vitro tests measuring proliferation, viability, clonogenicity, cell cycle and apoptosis. Moreover, using oligonucleotide microarrays and real-time PCR, we identified several genes whose expression changed after GAR and AA treatment. The examined HATi significantly reduce the invasive phenotype of RMS cells by inhibiting the growth rate, viability and clonogenic abilities. What is more, these substances cause cell cycle arrest in the G2/M phase, induce apoptosis and affect the genetic expression of the endoplasmic reticulum stress sensors. GAR and AA may serve as promising potential anti-cancer drugs since they sensitize the RMS cells to chemotherapeutic treatment.

Arginine methylation is considered to be one of the most permanent and one of the most frequent post-translational modifications. The reaction of transferring a methyl group from S-adenosylmethionine to arginine residue is catalyzed by aginine methyltransferase (PRMT). In humans there are nine members of the PRMT family, named in order of discovery of PRMT1- PRMT9. Arginine methyltransferases were divided into three classes: I, II, III, with regard to the product of the catalyzed reaction. The products of their activity are, respectively, the following: asymmetric dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA) and monomethylarginine (MMA). These modifications significantly affect the chromatin functions; therefore, they can act as co-activators or suppressors of the transcription process. Arginine methylation plays a crucial role in many biological processes in a human organism. Among others, it participates in signal transduction control, mRNA splicing and the regulation of basic cellular processes such as proliferation, differentiation, migration and apoptosis. There is increasing evidence that dysregulation of PRMT levels may lead to the cancer transformation of cells. The correlation between increased PRMT level and cancer has been demonstrated in the following: breast, ovary, lung and colorectal cancer. The activity of arginine methyltransferase can be regulated by small molecule PRMT inhibitors. To date, three substances that inhibit PRMT activity have been evaluated in clinical trials and exhibit anti-tumor activity against hematological cancer. It is believed that the use of specific PRMT inhibitors may become a new, effective and safe treatment of oncological diseases.