Hasmah Abdullah

The study investigated the effects of gallic acid (GA) and methyl gallate (MG), in combination with cisplatin (CIS), on apoptotic protein expression, antioxidant gene expression and cell migration in HeLa cervical cancer cells. HeLa cells were treated with the combinations CIS–GA and CIS–MG prior to further analysis. The expression of apoptotic proteins (Bax, Bcl-2, caspase-3, caspase-9 and p53) was determined via western blot analysis. Antioxidant gene expression in treated HeLa cells was then assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The migration-inhibitory effect of the compound combinations was assessed using a scratch wound-healing assay. Treatment with CIS–GA significantly upregulated the expression of p53, Bax, caspase-3 and caspase-9, and downregulated the expression of Bcl-2. Results from RT-qPCR revealed downregulation of human catalase (hCAT) in the CIS–GA group and no changes in superoxide dismutase 1 (SOD1) expression in either the CIS–GA or CIS–MG groups. Moreover, lower wound closure percentages were observed after 24-hour incubation in both treated groups, indicating inhibited cell migration. These findings suggest that GA and MG combined with CIS upregulate apoptotic proteins by downregulating antioxidant gene (hCAT).

Breast cancer is among the leading causes of cancer-related death in women worldwide. Cisplatin is a widely used chemotherapeutic drug because of its strong efficacy in killing various cancer cells. However, it presents several toxicity effects and development of drug resistance. Looking at these shortcomings, there is growing interest in combining conventional chemotherapeutic drugs with natural compounds. Therefore, a natural phenolic compound, methyl gallate, known to have strong anticancer and antioxidant properties, is a potential candidate for enhancing the therapeutic efficacy and reducing the side effects of current chemotherapy drugs. This study aims to determine the antiproliferative effect of methyl gallate and its combination with cisplatin on MCF-7 cells using MTT assay. The combination effect was evaluated using MTT assay and then analysed using CompuSyn software. Besides, this study was done to evaluate the morphology of apoptotic cells using AO/PI stain and to determine the ability of the combination treatment to inhibit the migration of MCF-7 cells using wound healing assay. The cell viability was inhibited dose-dependently with IC ₅₀ values of methyl gallate and cisplatin were 20.21 µg/mL and 13.38 µg/mL respectively. Methyl gallate at fixed concentration combined with the lowest concentration of cisplatin inhibited greater MCF-7 cell growth compared to cisplatin alone with a combination index value of less than 1 indicating the synergistic effect. The MCF-7 cells treated with single and combination drugs exhibited several apoptotic characteristics. Migration of MCF-7 cells was also significantly inhibited by single and combination treatments. In conclusion, this study suggested that methyl gallate in combination with cisplatin has a good potential to be developed as a chemotherapeutic agent for breast cancer.

(1) Introduction: Indonesia is vulnerable to climate change’s impact. To adapt better, a study about community knowledge, attitudes, and behavior toward climate change is needed. This research aims to determine the perception of the health impacts caused and how urban communities (in the Jakarta area) respond to climate change, using a cross-sectional study to see the relationship between knowledge and attitudes towards behavior related to climate change. (2) Methods: This study used descriptive, analytical, observational, and quantitative methods with a cross-sectional design. In addition, the procedures were conducted in the Jakarta metropolitan area using a Google Form platform distributed through social media. Univariate, bivariate, and multivariate analyses were performed using IBM SPSS Statistics 22 software. (3) Results: The results showed that attitudes had a significant association with behavior toward climate change. Respondents had good knowledge of climate change but had negative attitudes and bad behavior. In addition, the impacts felt by the community were increasing heat waves, air pollution, and worsening health conditions. Most respondents were confident and believed that Indonesia could withstand these impacts. (4) Conclusions: Respondents in this study showed good knowledge of climate change and had a positive attitude towards adaptation and mitigation of climate change impacts. However, this is not reflected in their behavior because they predominantly show poor results. The government should be able to encourage changes in people’s behavior so that they are better prepared to deal with the impacts of climate change.

Background: Uninhabited shophouses become breeding places for mosquitoes which cause high levels of dengue hemorrhagic fever (DHF), whereas the existence of squatters causes a reduction in green open space, one of which becomes a breeding place for Aedes sp. Methods: This study aimed to develop a DHF risk model in shophouses and squatters in Batam city. This research applied an ecological study design using a spatial approach with the geographically weighted regression (GWR) method. The variables studied were the incidence of dengue fever, vector density, and rainfall. Results: The results of the analysis show that for the vector density in the shophouses, the odds ratio (OR) was 4.71 while for the vector density in squatters, the OR was 6.76. For the rainfall in the shophouses, the OR was 0.83 while for the rainfall in the Squatters, the OR was 1.68. Model analysis shows that the higher shophouses and squatters can cause an increase in dengue cases. Conclusion: Risk analysis shows that factors that can increase DHF vulnerability include high vector density with a risk of 4.71 times (shophouses) and 6.76 times (squatters), and high rainfall in squatters with a risk of 1680 times. The distribution of dengue cases shows that Sambau dan Batu Selicin are subdistricts that have a high distribution of vulnerabilities in both shophouses and squatters. The mathematical model of dengue risk shows that every construction of one shophouse or one squatter can cause an increase in dengue cases by one case.

Melaleuca cajuputi plant has piqued the interest of researchers due to its pharmacological properties. However, there is scarce information regarding its enzyme inhibitory effects and possible mechanism of action. Thus, this study aimed to investigate the antioxidant, enzyme inhibitory, and potential binding interactions of bioactive components in M. cajuputi extract and fractions with the target enzymes. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging (DPPH) assay was used for the antioxidant activity. The enzyme inhibition potential was assessed using tyrosinase and acetylcholinesterase (AChE) enzymes. M. cajuputi methanolic extract (MCME) demonstrated the most potent scavenging activity in comparison to Melaleuca fraction (MF1) and (MF2), as evidenced by IC50 values of 28.14 ± 0.96, 35.26 ± 0.64, and 80.90 ± 0.17 μg/mL, respectively. Similarly, the results of the enzyme inhibition assay showed that the MCME (IC50 65.81± 0.39 μg/mL) had the highest potency on tyrosinase enzyme compared to MF1 (IC50 131.3± 0.43 μg/mL) and MF2 (IC50 215.3 ± 0.48 μg/mL). However, MF2 (IC50 3.35 ± 0.37 μg/mL) showed a remarkable AChE enzyme inhibition than MCME and MF1. On the other hand, MCME possessed a low toxicity effect with an LC50 of 781 ± 0.07 μg/mL, whereas MF1 and MF2 were non-toxic. The 10-methylanthracene-9-carboxaldehyde, 2-isopropyl-10-methylphenanthrene, 2-tert butylanthracene, β-eudesmol, and α-eudesmol showed a strong binding propensity ranging from -5.1 to -6.2 and -6.4 to -7.6 kcal/mol towards tyrosinase and AChE respectively. The leaf extract of M. cajuputi could be considered a novel source of naturally occurring antioxidants and promising enzyme inhibitors.

Background: Most cervical cancer fatalities have been reported due to drug resistance, invasion, and metastasis. Combination therapy is a prominent technique for overcoming the toxicity of cancer chemotherapy to normal cells, which is mediated across numerous targeted pathways and requires a lower dose of each individual agent. Polyphenolic substances have the potential to improve chemotherapy efficacy while also reducing negative effects. Aims: This study aimed to review the research findings on the role of reactive oxygen species (ROS) in cervical cancer cell HeLa treated with combination therapy. Results: Hydroxyl radicals damage DNA, causing a cascade of structural changes in purine and pyrimidine bases that could lead to mutagenicity. ROS, such as hydroxyl radical (OH-), superoxide anions (O2 -), hydrogen peroxide (H2O2), and peroxyl radicals (ROO-), are frequent products of aerobic metabolism that can be beneficial or detrimental to the biological system. To combat the harmful effects of ROS, cells have an antioxidative defense system that comprises superoxide dismutases, catalase, glutathione, and other defensive mechanisms. Excessive ROS accumulation causes DNA damage, which triggers the apoptotic machinery, resulting in cell death. Conclusion: Chemotherapeutic medications with phenolic compounds or polyphenol-rich extracts exhibit anticancer synergy. Combination treatment with polyphenols and anticancer drugs is one of the promising approaches in the treatment of cervical cancer.

Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC₅₀) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC₅₀ values. The IC₅₀ concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC₅₀ value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.