Predicting the possible effect of miR-203a-3p and miR-29a-3p on DNMT3B and GAS7 genes expression

Aberrant expression of genes involved in methylation, including DNA methyltransferase 3 Beta (DNMT3B), can cause hypermethylation of various tumor suppressor genes. In this regard, various molecular factors such as microRNAs can play a critical role in regulating these methyltransferase enzymes and eventually downstream genes such as growth arrest specific 7 (GAS7). Accordingly, in the present study we aimed to predict regulatory effect of miRNAs on DNMT3B and GAS7 genes expression in melanoma cell line. hsa-miR-203a-3p and hsa-miR-29a-3p were predicted and selected using bioinformatics software. The Real-time PCR technique was performed to investigate the regulatory effect of these molecules on the DNMT3B and GAS7 genes expression. Expression analysis of DNMT3B gene in A375 cell line showed that there was a significant increase compared to control (p value = 0.0015). Analysis of hsa-miR-203a-3p and hsa-miR-29a-3p indicated the insignificant decreased expression in melanoma cell line compared to control (p value < 0.05). Compared to control, the expression of GAS7 gene in melanoma cells showed a significant decrease (p value = 0.0323). Finally, our findings showed that the decreased expression of hsa-miR-203a-3p and hsa-miR-29a-3p can hypothesize that their aberrant expression caused DNMT3B dysfunction, possible methylation of the GAS7 gene, and ultimately decreased its expression. However, complementary studies are necessary to definite comment.

Study on the Anti-cancer Potential of Aegle marmelos Fruit Extract Pro and Anti Apoptotic Molecule in Human Melanoma Cell Line-A375

Aegle marmelos is also known as bael which is commonly found in south East Asia and Indian-sub continent. The origin of bael is India. Bael is also known as the golden apple, Bengal-quince in India. In the ancient medical system, Aegle marmelos play an important role and its extract is also useful in inflammation, diabetes, cancer and asthma. The leaves are used for anti-inflammatory, nervous disorder, control blood sugar and fruit is used to treat antiviral, anti-diabetics, and brain and heart tonic. In addition, studies have proved that bael is used for the treatment and prevention of cancer. The main aim of this study is to assess the anti-cancer potential of Aegle marmelos fruit extract pro and anti apoptotic molecules in human melanoma cell line-A375. In the present study, Human Melanoma A375 cells will be produced, grown and will be passed in different culture flasks, then RNA isolation was done and by reverse transcriptase process, RNA gets converted into cDNA. This cDNA will be used for the amplification of growth factor beta using gene specific primers by commercially available real time PCR kit. The anticancer potential effect was found in 400µg/ml, as the concentration increases, the cell viability is decreased. The current study explains the potential application of bael in pharmacological and medicinal uses in near future.

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

Potassium channels have emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large-conductance Ca2+-activated K+ channel, often referred to as BK channel, is involved in several cancer-associated processes. Here, we investigated the effects of different BK activators, NS-11021, NS-19504, and BMS-191011, in IGR39 (primary melanoma cell line) and Panc-1 (primary pancreatic duct carcinoma cell line), highly expressing the channel, and in IGR37 (metastatic melanoma cell line) that barely express BK. Our data showed that NS-11021 and NS-19504 potently activated BK channels in IGR39 and Panc-1 cells, while no effect on channel activation was detected in IGR37 cells. On the contrary, BK channel activator BMS-191011 was less effective. However, only NS-11021 showed significant effects in cancer-associated processes, such as cell survival, migration, and proliferation in these cancer cell lines. Moreover, NS-11021 led to an increase of intracellular Ca2+ concentration, independent of BK channel activation, thus complicating any interpretation of its role in the regulation of cancer-associated mechanisms. Overall, we conclude that the activation of the BK channel by itself is not sufficient to produce beneficial anti-cancer effects in the melanoma and PDAC cell lines examined. Importantly, our results raise an alarm flag regarding the use of presumably specific BK channel openers as anti-cancer agents.

Metformin Increases Sensitivity of Melanoma Cells to Cisplatin by Blocking Exosomal-Mediated miR-34a Secretion

Melanoma, also known as malignant melanoma, is a type of cancer derived from the pigment-containing cells known as melanocytes. Cisplatin (CDDP) is widely used in the treatment of different types of tumors with high response rates, but it generally has low efficiency in melanoma. This study aimed to investigate whether metformin could sensitize the melanoma cell line A375 to cisplatin. Our results for the first time indicated that CDDP increased the miR-34a secretion by exosomes in melanoma A375 cells, which was, at least partially, related to the cisplatin resistance of melanoma cells. Moreover, metformin significantly sensitized A375 cells to cisplatin. Mechanistically, metformin significantly blocked the exosome-mediated miR-34a secretion induced by cisplatin. Our study not only reveals a novel mechanism that exosomal secretion of miR-34a is involved in the cisplatin resistance of melanoma cells but also provides a promising therapeutic strategy by synergistic addition of metformin.

The effect of extraction solvent polarity on cytotoxic properties of Sargassum crassifolium against B16-F10 melanoma cancer cell model

Abstract.The prevalence of skin cancer continues to increase from year to year. Skin cancer mainly caused bymelanin accumulation on the skin surface (hyperpigmentation) or excessive melanogenesisoccurs. The brown macroalgae S. crassifolium is one of marine natural resources which is abundant in Lombok, Indonesia coastal areas. However, information regarding its potential bioactive activities remains limited. This study aims to evaluate the effective extraction solvent for S. crassifolium for gaining optimum bioactive compounds with promising cytotoxμic activity against melanoma cell line. The three variations of the solvent used are ethanol, n-hexane, and ethyl acetate. Some major compounds that were detected by GC-MS analysis in S. crassifolium were state as follow: n-Hexadecanoic acid (Palmitic acid), Hexadecanoic acid, methyl ester (Methyl palmitate), Oleic Acid, Dodecanoic acid, methyl ester, 9-Octadecenoic acid, methyl ester, Tetradecanoic acid, methyl ester. SEA showed the higher amount of methyl palmitate compared toS. crassifolium extracted with other solvent. Accordingly, to the major chemical constituent, SEA showed highest IC50 against melanoma cell line (61.26 ± 2.13 μg/mL) compared to SET and SNX. SEA also induced apoptosis which characterized by increase in apoptotic nuclei.