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Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, How CW, et al.

J Ethnopharmacol, 2015 May 26;166:270-8.
PMID: 25797115 DOI: 10.1016/j.jep.2015.03.039

Dillenia suffruticosa (Family: Dilleniaceae) or commonly known as "Simpoh air" in Malaysia, is traditionally used for treatment of cancerous growth including breast cancer.
Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway

Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.

J Ethnopharmacol, 2016 Dec 24;194:549-558.
PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.
AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.
MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.
RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.
CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.
Fulltext The influence of system quality characteristics on health care providers' performance: Empirical evidence from Malaysia

Mohd Salleh MI, Zakaria N, Abdullah R

J Infect Public Health, 2016 Nov-Dec;9(6):698-707.
PMID: 27659115 DOI: 10.1016/j.jiph.2016.09.002

BACKGROUND: The Ministry of Health Malaysia initiated the total hospital information system (THIS) as the first national electronic health record system for use in selected public hospitals across the country. Since its implementation 15 years ago, there has been the critical requirement for a systematic evaluation to assess its effectiveness in coping with the current system, task complexity, and rapid technological changes. The study aims to assess system quality factors to predict the performance of electronic health in a single public hospital in Malaysia.

METHODS: Non-probability sampling was employed for data collection among selected providers in a single hospital for two months. Data cleaning and bias checking were performed before final analysis in partial least squares-structural equation modeling.

RESULTS AND CONCLUSIONS: Convergent and discriminant validity assessments were satisfied the required criterions in the reflective measurement model. The structural model output revealed that the proposed adequate infrastructure, system interoperability, security control, and system compatibility were the significant predictors, where system compatibility became the most critical characteristic to influence an individual health care provider's performance. The previous DeLone and McLean information system success models should be extended to incorporate these technological factors in the medical system research domain to examine the effectiveness of modern electronic health record systems. In this study, care providers' performance was expected when the system usage fits with patients' needs that eventually increased their productivity.
Fulltext Monte Carlo dose calculation in dental amalgam phantom

Aziz MZ, Yusoff AL, Osman ND, Abdullah R, Rabaie NA, Salikin MS

J Med Phys, 2015 Jul-Sep;40(3):150-5.
PMID: 26500401 DOI: 10.4103/0971-6203.165080

It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation.
Preferences and Experiences of Muslim Patients and Their Families in Muslim-Majority Countries for End-of-Life Care: A Systematic Review and Thematic Analysis

Abdullah R, Guo P, Harding R

J Pain Symptom Manage, 2020 12;60(6):1223-1238.e4.
PMID: 32659320 DOI: 10.1016/j.jpainsymman.2020.06.032

BACKGROUND: Care for people with progressive illness should be person centered and account for their cultural values and spiritual beliefs. There are an estimated 1.7 billion Muslims worldwide, largely living in low-income and middle-income countries.
AIMS: This study aimed to identify, appraise, and integrate the evidence for the experiences and preferences of Muslim patients and/or families for end-of-life care in Muslim-majority countries.
DESIGN: Systematic review.
DATA SOURCES: PsychINFO, MEDLINE, Embase, Global Health, CINAHL, Cochrane Library and Registry of Clinical Trials, PubMed, Applied Social Sciences Index and Abstracts (ASSIA), Social Services Abstracts, Sociological Abstracts, Social Policy & Practice, and Scopus were searched until December 2018. Handsearching was performed, and gray literature was included. Qualitative studies analyzed using thematic analysis and quantitative component provided triangulation.
RESULTS: The initial search yielded n = 5098 articles, of which n = 30 met the inclusion criteria. A total of 5342 participants (4345 patients; 81.3%) were included; 97.6% had advanced cancer. Most (n = 22) studies were quantitative. Three themes and subthemes from qualitative studies were identified using thematic analysis: selflessness (burden to others and caregiver responsibilities), ambivalence (hope and hopelessness), and strong beliefs in Islam (beliefs in death and afterlife and closeness to Allah). Qualitative studies reported triangulation; demonstrating conflicts in diagnosis disclosure and total pain burden experienced by both patients and families.
CONCLUSION: Despite the scarce evidence of relatively low quality, the analysis revealed core themes. To achieve palliative care for all in line with the total pain model, beliefs must be identified and understood in relation to decision-making processes and practices.
Developing a nutrition education package for Malaysian hemodialysis patients

Karupaiah T, Swee CS, Abdullah R

J Ren Nutr, 2001 Oct;11(4):220-7.
PMID: 11680003

To develop an education package with uniform nutrition messages appropriate for Malaysian patients undergoing hemodialysis.
Rare k-mer DNA: Identification of sequence motifs and prediction of CpG island and promoter

Mohamed Hashim EK, Abdullah R

J Theor Biol, 2015 Dec 21;387:88-100.
PMID: 26427337 DOI: 10.1016/j.jtbi.2015.09.014

Empirical analysis on k-mer DNA has been proven as an effective tool in finding unique patterns in DNA sequences which can lead to the discovery of potential sequence motifs. In an extensive study of empirical k-mer DNA on hundreds of organisms, the researchers found unique multi-modal k-mer spectra occur in the genomes of organisms from the tetrapod clade only which includes all mammals. The multi-modality is caused by the formation of the two lowest modes where k-mers under them are referred as the rare k-mers. The suppression of the two lowest modes (or the rare k-mers) can be attributed to the CG dinucleotide inclusions in them. Apart from that, the rare k-mers are selectively distributed in certain genomic features of CpG Island (CGI), promoter, 5' UTR, and exon. We correlated the rare k-mers with hundreds of annotated features using several bioinformatic tools, performed further intrinsic rare k-mer analyses within the correlated features, and modeled the elucidated rare k-mer clustering feature into a classifier to predict the correlated CGI and promoter features. Our correlation results show that rare k-mers are highly associated with several annotated features of CGI, promoter, 5' UTR, and open chromatin regions. Our intrinsic results show that rare k-mers have several unique topological, compositional, and clustering properties in CGI and promoter features. Finally, the performances of our RWC (rare-word clustering) method in predicting the CGI and promoter features are ranked among the top three, in eight of the CGI and promoter evaluations, among eight of the benchmarked datasets.
Fulltext Comparative aspects of microRNA expression in canine and human cancers

Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC

J Vet Sci, 2018 Mar 31;19(2):162-171.
PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
Encapsulation of Bacillus salmalaya 139SI using double coating biopolymer technique

Vejan P, Abdullah R, Khadiran T, Ismail S

Lett Appl Microbiol, 2019 Jan;68(1):56-63.
PMID: 30339728 DOI: 10.1111/lam.13088

Sustainable crop production for a rapidly growing human population is one of the current challenges faced by the agricultural sector. However, many of the chemical agents used in agriculture can be hazardous to humans, non-targeted organism and environment. Plant growth promoting rhizobacteria have demonstrated a role in promoting plant growth and health under various stress conditions including disease. Unfortunately, bacterial viability degrades due to temperature and other environmental factors (Bashan et al., Plant Soil 378: 1-33, 2014). Encapsulation of bacteria into core-shell biopolymers is one of the promising techniques to overcome the problem. This study deals with the encapsulation of Bacillus salmalaya 139SI using simple double coating biopolymer technique which consist of brown rice protein/alginate and 0·5% low molecular weight chitosan of pH 4 and 6. The influence of biopolymer to bacteria mass ratio and the chitosan pH on the encapsulation process, physic-chemical, morphology and bioactivity properties of encapsulated B. salmalaya 139SI have been studied systematically. Based on the analysis of physico-chemical, morphology and bioactivity properties, B. salmalaya 139S1 encapsulated using double coating encapsulation technology has promising viability pre- and postfreeze-drying with excellent encapsulation yields of 99·7 and 89·3% respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The need of a simple yet effective way of encapsulating plant growth promoting rhizobacteria is crucial to further improve their benefits to global sustainable agriculture practice. Effective encapsulation allows for protection, controlled release and function of the micro-organism, as well as providing a longer shelf life for the product. This research report offers an innovative yet simple way of encapsulating using double coating technology with environmentally friendly biopolymers that could degrade and provide nutrients when in soil. Importantly, the bioactivity of the bacteria is maintained upon encapsulation.
Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo

Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Aspollah Sukari M, Abdullah R, et al.

Leuk. Res., 2010 Nov;34(11):1483-92.
PMID: 20569984 DOI: 10.1016/j.leukres.2010.04.023

Typhonium flagelliforme (TF) is a tropical plant, traditionally used by the ethnic population of Malaysia for the cure of various cancers. This plant had shown to induce antiproliferative effect as well as apoptosis in cancer cells. However, there is no available information to address that TF affects murine leukemia cells in vitro and in vivo. Here, we investigated in vitro and in vivo effects of TF on murine leukemia WEHI-3 cells. It was found that the growth of leukemia cells in vitro was inhibited by the various extracts of TF. Among these fractions, the dichloromethane (DCM) tuber extracts of TF showed the lowest IC(50) (24.0 ± 5.2 μg/ml) and had demonstrated apoptogenic effect when observed under fluorescent microscope. We investigated the in vivo effects of DCM tuber extracts of TF on murine leukemia cells, and the results showed that the counts of immature granulocytes and monocytes were significantly decreased in peripheral blood of BALB/c leukemia mice after the oral administration of DCM tuber extracts of TF for 28 days with three doses (200, 400 and 800 mg/kg). These results were confirmed by observing the spleen histopathology and morphology of enlarged spleen and liver in leukemia mice when compared with the control. Furthermore, the cell death mechanism in the spleen tissue of treated mice was found via apoptosis.
Fulltext Nutritional assessment of pre-school children in rural villages of the family dynamics, lifestyles and nutrition study (1997-2001) I. Socio-economic status of households

Chee HL, Khor G, Arshad F, Wanmuda W, Shabdin A, Abusamah A, et al.

Malays J Nutr, 2002 Mar;8(1):13-31.
PMID: 22692437

This paper presents the socio-economic profile of households in the Family Dynamics Study (FDS) (1997-2001) and makes comparisons with the earlier Functional Groups Study (FGS) (1992-1996). For the current study, FGS villages with a high prevalence of child malnutrition were purposively selected. In each village selected, all households were included, and interviews with a structured questionnaire were conducted in April-May 1998. Incomes were generally low and incidence of poverty was high; 49.6% of the households were under the poverty line income, of which 37.2% were poor and 12.4% were hard core poor. Overall, only 23.2% of heads of households were in agricultural occupations, others being primarily waged workers and petty traders. Livestock rearing was widespread (57.8%), and most households (90.4%) owned at least one motorised vehicle, the most common being the motorcycle. The majority of households had refrigerators (73.6%), washing machines (58.8%), and televisions (91.1%); but telephones (42.2%), mobile phones (6.1%) and computers (2.3%) were less common. Although 99.7% of households had electricity supply and 95.1% had either a flush or pour flush latrine, only 57.4% had piped water supply. In comparison to the FGS, poverty in the current study is lower (49.6% of FDS households are poor compared to 55.2% of FGS households), the proportion of household heads in agricultural occupations is also lower (26.9% compared to 55.3%), while all other socioeconomic indicators were better, except for piped water supply, which remains inadequate for households in the current study.
Evaluation of heavy metals and environmental risk assessment in the Mangrove Forest of Kuala Selangor estuary, Malaysia

ELTurk M, Abdullah R, Rozainah MZ, Abu Bakar NK

Mar Pollut Bull, 2018 Nov;136:1-9.
PMID: 30509789 DOI: 10.1016/j.marpolbul.2018.08.063

This study was carried out to evaluate the distribution, enrichment and ecological risk of heavy metals (arsenic (As), zinc (Zn), manganese (Mn), copper (Cu) and lead (Pb)) concentration in Kuala Selangor estuary at the Kuala Selangor Nature Park. The results suggested that As and Pb in sediment were as high as the background value, suggesting the presence of anthropogenic contamination. The risk assessment of sediment Igeo, CD, and PERI, on the other hand, showed low risk of heavy metals in Kuala Selangor estuary. Meanwhile, risk assessment code (RAC) results showed that Mn, As and Zn presented medium to high level of environmental risk. The translocation factor and bioaccumulation factors of heavy metal concentration by mangrove vegetation showed a variety of trends, which indicates the different partitioning and uptake ability of heavy metal in the tissues of different mangrove species. Therefore, underscores the importance of preserving the high diversity of mangroves at securing the health and productivity of the coastal region. These results may play a critical role in facilitating decision makers in managing the sustainability of mangrove forests.
Fulltext Investigation of Ion Transport Parameters and Electrochemical Performance of Plasticized Biocompatible Chitosan-Based Proton Conducting Polymer Composite Electrolytes

Hadi JM, Aziz SB, R Saeed S, Brza MA, Abdulwahid RT, Hamsan MH, et al.

Membranes (Basel), 2020 Nov 21;10(11).
PMID: 33233480 DOI: 10.3390/membranes10110363

In this study, biopolymer composite electrolytes based on chitosan:ammonium iodide:Zn(II)-complex plasticized with glycerol were successfully prepared using the solution casting technique. Various electrical and electrochemical parameters of the biopolymer composite electrolytes' films were evaluated prior to device application. The highest conducting plasticized membrane was found to have a conductivity of 1.17 × 10-4 S/cm. It is shown that the number density, mobility, and diffusion coefficient of cations and anions fractions are increased with the glycerol amount. Field emission scanning electron microscope and Fourier transform infrared spectroscopy techniques are used to study the morphology and structure of the films. The non-Debye type of relaxation process was confirmed from the peak appearance of the dielectric relaxation study. The obtained transference number of ions (cations and anions) and electrons for the highest conducting sample were identified to be 0.98 and 0.02, respectively. Linear sweep voltammetry shows that the electrochemical stability of the highest conducting plasticized system is 1.37 V. The cyclic voltammetry response displayed no redox reaction peaks over its entire potential range. It was discovered that the addition of Zn(II)-complex and glycerol plasticizer improved the electric double-layer capacitor device performances. Numerous crucial parameters of the electric double-layer capacitor device were obtained from the charge-discharge profile. The prepared electric double-layer capacitor device showed that the initial values of specific capacitance, equivalence series resistance, energy density, and power density are 36 F/g, 177 Ω, 4.1 Wh/kg, and 480 W/kg, respectively.
The application of naked DNA plasmid (DrZP3) and recombinant adenovirus (Ad-rZP3) in rat animal model to determine comparative efficacy of ZP3-Immunocontraceptive vaccines

Mohd-Lila MA, Yee LK, Cen LS, Bala JA, Balakrishnan KN, Allaudin ZN, et al.

Microb Pathog, 2019 Sep;134:103572.
PMID: 31163251 DOI: 10.1016/j.micpath.2019.103572

The common physical and chemical methods for controlling rat pest are less than satisfactory and inhumane. Immunocontraception approach has been considered more humane and it can be accomplished by inducing the relevant host immune response that block further development of reproductive gametes. ZP3 proteins are known to play very important role during sperm-ovum fertilization. It is a self-antigen and only localized in female ovaries. Therefore, an immunization with ZP3 protein elsewhere will induce a generalize host immune response against ZP3 protein. This study employed rat ZP3 (rZP3) gene prepared from its cDNA of Rattus rattus diardii. It was delivered and expressed in vivo by naked plamid DNA (DrZP3) or recombinant ZP3-Adenovirus (Ad-rZP3). Expression studies in vitro with DrZP3 or Ad-ZP3 showed rZP3 proteins were successfully expressed in Vero cells. Hyperimmune serum against rZP3 that were prepared by immunizing several rats with purified rZP3-pichia yeast fusion protein showed it blocked sperms from binding DrZP3-transfected Vero cells. Female Sprague Dawley rats immunized with DrZP3 demonstrated a long-term effect for significant reduction of fertility up to 92.6%. Ovaries from rats immunized with DrZP3 were severely atrophied with disappearance of primordial follicles from ovarian cortex with an increased in the amount of oocyte-free cell clusters. Female rats immunized with Ad-rZP3 demonstrated 27% reduction of fertility. The infertility induced by Ad-rZP3 is comparatively low and ineffective. This could be due to a strong host immune response that suppresses the recombinant virus itself resulted in minimum rZP3 protein presentation to the host immune system. As a result, low antibody titers produced against rZP3 is insufficient to block oocytes from maturity and fertilization. Therefore, immunization with DrZP3 for immunocontraception is more effective than Ad-rZP3 recombinant adenovirus. It is proposed to explore further on the use of adenovirus or other alternative viruses to deliver ZP3 protein and for the development of enhanced expression of rZP3 in target host.
Effect of recombinant human erythropoietin and doxorubicin in combination on the proliferation of MCF-7 and MDA-MB231 breast cancer cells

Radwan EM, Abdullah R, Al-Qubaisi MS, El Zowalaty ME, Naadja SE, Alitheen NB, et al.

Mol Med Rep, 2016 May;13(5):3945-52.
PMID: 26987078 DOI: 10.3892/mmr.2016.4989

Patients with cancer often exhibit signs of anemia as the result of the disease. Thus, cancer chemotherapies often include erythropoietin (EPO) in the regime to improve the survival rate of these patients. The aim of the present study was to determine the effect of EPO on doxorubicin-treated breast cancer cells. The cytotoxicity of doxorubicin alone or in combination with EPO against the MCF-7 and MDA-MB‑231 human breast cancer cells were determined using an MTT cell viability assay, neutral red (NR) uptake assay and lactate dehydrogenase (LDH) assay. The estimated half maximal inhibitory concentration values for doxorubicin and the combination of doxorubicin with EPO were between 0.140 and 0.260 µg/ml for all cells treated for 72 h. Treatment with doxorubicin in combination with EPO led to no notable difference in cytotoxicity, compared with treatment with doxorubicin alone. The antiproliferative effect of doxorubicin at a concentration of 1 µg/ml on the MDA‑MB‑231 cells was demonstrated by the decrease in viable cells from 3.6x10(5) at 24 h to 2.1x10(5) at 72 h of treatment. In order to confirm apoptosis in the doxorubicin-treated cells, the activities of caspases-3/7 and ‑9 were determined using a TBE assay. The results indicated that the activities of caspases-3/7 and ‑9 were significantly elevated in the doxorubicin-treated MDA-MB-231 cells by 571 and 645%, respectively, and in the MCF 7 cells by 471 and 345%, respectively, compared with the control cells. EPO did not modify the effect of doxorubicin on these cell lines. The results of the present study suggested that EPO was safe for use in combination with doxorubicin in the treatment of patients with breast cancer and concurrent anemia.
Fulltext In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica

Malami I, Abdul AB, Abdullah R, Bt Kassim NK, Waziri P, Christopher Etti I

Molecules, 2016 Apr 08;21(4):417.
PMID: 27070566 DOI: 10.3390/molecules21040417

Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development.
Fulltext Role of Plant Growth Promoting Rhizobacteria in Agricultural Sustainability-A Review

Vejan P, Abdullah R, Khadiran T, Ismail S, Nasrulhaq Boyce A

Molecules, 2016 Apr 29;21(5).
PMID: 27136521 DOI: 10.3390/molecules21050573

Plant growth promoting rhizobacteria (PGPR) shows an important role in the sustainable agriculture industry. The increasing demand for crop production with a significant reduction of synthetic chemical fertilizers and pesticides use is a big challenge nowadays. The use of PGPR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth through either a direct or indirect mechanism. The mechanisms of PGPR include regulating hormonal and nutritional balance, inducing resistance against plant pathogens, and solubilizing nutrients for easy uptake by plants. In addition, PGPR show synergistic and antagonistic interactions with microorganisms within the rhizosphere and beyond in bulk soil, which indirectly boosts plant growth rate. There are many bacteria species that act as PGPR, described in the literature as successful for improving plant growth. However, there is a gap between the mode of action (mechanism) of the PGPR for plant growth and the role of the PGPR as biofertilizer-thus the importance of nano-encapsulation technology in improving the efficacy of PGPR. Hence, this review bridges the gap mentioned and summarizes the mechanism of PGPR as a biofertilizer for agricultural sustainability.
Fulltext Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Rahim NFC, Hussin Y, Aziz MNM, Mohamad NE, Yeap SK, Masarudin MJ, et al.

Molecules, 2021 Feb 26;26(5).
PMID: 33652694 DOI: 10.3390/molecules26051261

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012-2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.
Fulltext Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model

Nordin N, Yeap SK, Rahman HS, Zamberi NR, Mohamad NE, Abu N, et al.

Molecules, 2020 Jun 09;25(11).
PMID: 32526880 DOI: 10.3390/molecules25112670

Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.
Fulltext Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay

Vawhal PK, Jadhav SB, Kaushik S, Panigrahi KC, Nayak C, Urmee H, et al.

Molecules, 2023 Jan 19;28(3).
PMID: 36770672 DOI: 10.3390/molecules28031004

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

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