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Tannic acid enhances cisplatin effect on cell proliferation and apoptosis of human osteosarcoma cell line (U2OS)

Kasiram MZ, Hapidin H, Abdullah H, Hashim NM, Azlina A, Sulong S

Pharmacol Rep, 2022 Feb;74(1):175-188.
PMID: 34652600 DOI: 10.1007/s43440-021-00330-3

BACKGROUND: The increase in cases of chemoresistance of cisplatin for osteosarcoma treatment has called for the need to establish a new treatment regime. Tannic acid (TA) possesses a potent antiproliferative effect against various cancers. Therefore, this study investigated the effect of TA combined with cisplatin on human osteosarcoma cell lines (U2OS).
METHODS: MTT assay was used to determine the half-maximal inhibitory concentration (IC50), while the combination index (CI) value was utilized to analyze the interaction within each combination. The antiproliferative effect of the treatment was evaluated by trypan blue exclusion assay. The morphological changes of cells were observed under a phase-contrast inverted microscope. The nuclear morphology and percentage of apoptosis cells were evaluated by using the Hoechst 33258 staining and annexin V/PI assay, respectively.
RESULTS: The U2OS cells showed cytotoxic effect when treated with TA and cisplatin, with IC50 at 4.47 µg/mL and 16.25 µg/mL, respectively. The TA demonstrated no significant inhibition effect on the normal human fetal osteoblast cells (hFOB 1.19); yet, interestingly, a potent proliferative effect was indicated. Synergistic interaction was triggered when TA was combined with cisplatin at percentage ratios of 90:10 and 85:15. Meanwhile, antagonistic interaction was induced in the combination at percentage ratios of 75:25 and 50:50. On the other hand, a significant antiproliferative effect with prominent morphological alteration was detected in the cells treated with a combination of TA and cisplatin at the percentage ratio of 90:10. Additionally, combination-treated cells demonstrated the highest percentage of apoptosis cells, with distinct chromosomal condensation, nuclear fragmentation, reduction of nuclear volume, and notable apoptotic body.
CONCLUSION: Therefore, there is a high potential for the inclusion of TA in the cisplatin-based chemotherapeutic regimen of osteosarcoma.
Fulltext The impact of a pressure ulcer prevention educational program based on the health belief model for persons with spinal cord injury

Hashim NM, Engkasan JP, Hasnan N

J Spinal Cord Med, 2022 Nov;45(6):898-906.
PMID: 33465010 DOI: 10.1080/10790268.2020.1860868

STUDY DESIGN: Pre- and post- trial.
OBJECTIVES: To determine the changes of health belief levels after a pressure ulcer (PrU) prevention educational program based on the Health Belief Model (HBM).
SETTING: Department of Rehabilitation Medicine, University Medical Centre, Malaysia.
METHODS: This study was conducted between May 2016 and May 2018. We created a multidisciplinary structured PrU prevention education program based on the HBM, consisting of didactic lectures, open discussions and a practical session. The content of the program was based on several PrU prevention guidelines. The education program focused on a group of 6-10 participants, and was conducted by a multidisciplinary team; i.e. doctor, physiotherapist, occupational therapist and a nurse. The skin care belief scales (SCBS) questionnaire was administered pre, post and 8-week post intervention, which measured the 9 domains of HBM. The data from the study was analyzed using repeated measures ANOVA to assess the effectiveness of the program.
RESULTS: Thirty spinal cord injured participants who fulfilled the inclusion and exclusion criteria completed this study. The results of the education program show statistically significant effects on Susceptibility; F (2,58) = 12.53, P < 0.05, Barriers to Skin Check Belief; F(2,58) = 5.74, P > 0.05, Benefits to Wheelchair Pressure Relief Belief; F(1.65,47.8) = 3.97, P < 0.05, Barriers to Turning and Positioning Belief; F(2,58) = 3.92, P
Fulltext The impact of curcumin-graphene based nanoformulation on cellular interaction and redox-activated apoptosis: An in vitro colon cancer study

Al-Ani LA, Kadir FA, Hashim NM, Julkapli NM, Seyfoddin A, Lu J, et al.

Heliyon, 2020 Nov;6(11):e05360.
PMID: 33163675 DOI: 10.1016/j.heliyon.2020.e05360

Natural plants derivatives have gained enormous merits in cancer therapy applications upon formulation with nanomaterials. Curcumin, as a popular research focus has acquired such improvements surpassing its disadvantageous low bioavailability. To this point, the available research data had confirmed the importance of nanomaterial type in orienting cellular response and provoking different toxicological and death mechanisms that may range from physical membrane damage to intracellular changes. This in turn underlines the poorly studied field of nanoformulation interaction with cells as the key determinant in toxicology outcomes. In this work, curcumin-AuNPs-reduced graphene oxide nanocomposite (CAG) was implemented as a model, to study the impact on cellular membrane integrity and the possible redox changes using colon cancer in vitro cell lines (HT-29 and SW-948), representing drug-responsive and resistant subtypes. Morphological and biochemical methods of transmission electron microscopy (TEM), apoptosis assay, reactive oxygen species (ROS) and antioxidants glutathione and superoxide dismutase (GSH and SOD) levels were examined with consideration to suitable protocols and vital optimizations. TEM micrographs proved endocytic uptake with succeeding cytoplasm deposition, which unlike other nanomaterials studied previously, conserved membrane integrity allowing intracellular cytotoxic mechanism. Apoptosis was confirmed with gold-standard morphological features observed in micrographs, while redox parameters revealed a time-dependent increase in ROS accompanied with regressive GSH and SOD levels. Collectively, this work demonstrates the success of graphene as a platform for curcumin intracellular delivery and cytotoxicity, and further highlights the importance of suitable in vitro methods to be used for nanomaterial validation.
Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.

PLoS One, 2017;12(8):e0182357.
PMID: 28771532 DOI: 10.1371/journal.pone.0182357

Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
Translation and validation of the Malay version of modified orthotics and prosthetics users' survey

Hashim NM, Che Daud AZ, Ibrahim AH, Ab Majid MH, Mohd Ghazali MN, Abdul Razak MM, et al.

Prosthet Orthot Int, 2024 Jan 01;48(1):89-99.
PMID: 37639558 DOI: 10.1097/PXR.0000000000000270

BACKGROUND: An excellent validated and reliable instrument is paramount in holistically evaluating the prosthetic and orthotic (P&O) service, encompassing functional outcomes, health-related quality of life (HRQoL), and patient satisfaction with devices and service.
OBJECTIVE: To perform a translation and cross-cultural adaptation of 3 modules of the Orthotics and Prosthetics Users' Survey (OPUS): (1) lower-extremity functional status (LEFS), (2) client satisfaction with device and services (CSDS), and (3) HRQoL in Malay language, and analyze its psychometric properties.
STUDY DESIGN: Translation and validation study.
METHODS: This translation process consisted of 4 phases: (1) a forward-backward translation, (2) content and face validity by utilizing content and face validity indices, (3) pilot testing and psychometric analysis using exploratory factor analysis, and (4) test-retest reliability.
RESULTS: One item from OPUS Health Quality of Life Index-Malay pilot version, 5 items from OPUS LEFS-Malay pilot version, and 4 items of OPUS Satisfaction with Device and Services-Malay pilot version were deleted because of poor factor loading of <0.6. The final version of Modified OPUS HRQoL-M, Modified OPUS LEFS-M, and Modified OPUS CSDS-M consisted of 22 items, 15 items, and 17 items, respectively. The final versions of all 3 Modified OPUS Malay version possess good internal consistency of 0.854, 0.927, and 0.98, and intraclass correlation of 0.773, 0.871, and 0.821, respectively .
CONCLUSION: Modified OPUS HRQoL-M, Modified OPUS LEFS-M, and Modified OPUS CSDS-M are valid and reliable instruments to be adopted into the local Malaysia population.
Fulltext Two new acridone alkaloids from Glycosmis macrantha

Yahayu MA, Rahmani M, Hashim NM, Amin MA, Ee GC, Sukari MA, et al.

Molecules, 2011 May 27;16(6):4401-7.
PMID: 21623311 DOI: 10.3390/molecules16064401

Extraction and chromatographic separation of the extracts of dried stem barks of Glycosmis macrantha lead to isolation of two new acridone alkaloids, macranthanine and 7-hydroxynoracronycine, and a known acridone, atalaphyllidine. The structures of these alkaloids were determined by detailed spectral analysis and also by comparison with reported data.
Venuloxanthone, a new pyranoxanthone from the stem bark of Calophyllum venulosum

Bin Ismail AA, Ee GC, Bin Daud S, Teh SS, Hashim NM, Awang K

J Asian Nat Prod Res, 2015;17(11):1104-8.
PMID: 26023810 DOI: 10.1080/10286020.2015.1047353

A new pyranoxanthone, venuloxanthone (1), was isolated from the stem bark of Calophyllum venulosum, together with three other xanthones, tovopyrifolin C (2), ananixanthone (3) and caloxanthone I (4), along with two common triterpenes, friedelin (5) and lupeol (6). The structures of these compounds were identified using several spectroscopic analyses which are NMR, GCMS and FTIR experiments.
Fulltext α -Mangostin from Cratoxylum arborescens (Vahl) Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study

Sidahmed HM, Abdelwahab SI, Mohan S, Abdulla MA, Mohamed Elhassan Taha M, Hashim NM, et al.

Evid Based Complement Alternat Med, 2013;2013:450840.
PMID: 23634169 DOI: 10.1155/2013/450840

Cratoxylum arborescens (Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) of α -mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation of C. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigated in vitro. AM (10 and 30 mg/kg) inhibited significantly (P < 0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effective in vitro anti-H. pylori activity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity of α -mangostin.
Fulltext α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo

Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, et al.

Drug Des Devel Ther, 2014;8:1629-47.
PMID: 25302018 DOI: 10.2147/DDDT.S66105

Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.
β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo

Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.

J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051

The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.

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