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Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines

Fauzi AN, Norazmi MN, Yaacob NS

Food Chem Toxicol, 2011 Apr;49(4):871-8.
PMID: 21167897 DOI: 10.1016/j.fct.2010.12.010

Honey is reported to contain various compounds such as phenols, vitamins and antioxidants. The present study investigates the anticancer potential of Tualang honey (Agromas) (TH) in human breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines; as well as in the normal breast epithelial cell line, MCF-10A. The cells were treated with increasing doses of TH (1-10%) for up to 72 h. Increase in lactate dehydrogenase (LDH) leakage from the cell membranes indicates that TH is cytotoxic to all three cancer cells with effective concentrations (EC(50)) of 2.4-2.8%. TH is however, not cytotoxic to the MCF-10A cells. Reactivity with annexin V fluorescence antibody and propidium iodide as analysed by flow cytometry and fluorescence microscopy shows that apoptosis occurred in these cancer cells. TH also reduced the mitochondrial membrane potential (Δψ(m)) in the cancer cell lines after 24h of treatment. The activation of caspase-3/7 and -9 was observed in all TH-treated cancer cells indicating the involvement of mitochondrial apoptotic pathway. This study shows that TH has significant anticancer activity against human breast and cervical cancer cell lines.
Fulltext 2-Methoxy-1,4-Naphthoquinone (MNQ) Inhibits Glucose Uptake and Lactate Production in Triple-Negative Breast Cancer Cells

Daud SM, Yaacob NS, Fauzi AN

Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):59-65.
PMID: 33576213 DOI: 10.31557/APJCP.2021.22.S1.59

OBJECTIVE: The persistent activation of aerobic glycolysis in cancer cells results in accumulation of lactate and other metabolic intermediates that contribute to tumorigenesis. Increased glycolysis is frequently dysregulated in triple-negative breast cancer (TNBC), which promotes tumor growth and immune escape. This study was conducted to investigate the effect of 2-methoxy-1, 4-naphthoquinone (MNQ), compound extracted from Impatiens balsamina on glycolytic activities in human breast adenocarcinoma, MDA-MB-231 cells.
METHODS: Initially, MTT proliferation assay was used to test the cell viability with various doses of MNQ (5-100 µM). As the half maximal inhibitory concentration (IC50) was obtained, glucose uptake and lactate assays of the cells were tested with IC50 dose of MNQ. The treated cells were also subjected to gene and protein analysis of glycolysis-related molecules (GLUT1 and Akt).
RESULTS: The results showed that MNQ decreased the percentage of MDA-MB-231 cell viability in a dose-dependent manner with the IC50 value of 29 µM. The percentage of glucose uptake into the cells and lactate production decreased significantly after treatment with MNQ as compared to untreated cells. Remarkably, the expressions of GLUT1 and Akt molecules decreased in MNQ-treated cells, suggesting that the inhibition of glycolysis by MNQ is GLUT1-dependent and possibly mediated by the Akt signaling pathway.
CONCLUSION: Our findings indicate the ability of MNQ to inhibit the glycolytic activities as well as glycolysis-related molecules in MDA-MB-231 cells, suggesting the potential of MNQ to be further developed as an effective anticancer agent against TNBC cells.
Antiglycolytic Activities of Strobilanthes crispus Active Fraction and its Bioactive Components on Triple-Negative Breast Cancer Cells In Vitro

Muhammad SNH, Yaacob NS, Safuwan NAM, Fauzi AN

Anticancer Agents Med Chem, 2021 Apr 26.
PMID: 33906591 DOI: 10.2174/1871520621666210427104804

BACKGROUND: Survival and progression of cancer cells are highly dependent on aerobic glycolysis. Strobilanthes crispus has been shown to have promising anticancer effects on breast cancer cells. The involvement of the glycolysis pathway in producing these effects is unconfirmed, thus further investigation is required to elucidate this phenomenon.
OBJECTIVE: This study aims to determine the effect of S. crispus active fraction (F3) and its bioactive components on glycolysis in triple-negative breast cancer cells (MDA-MB-231).
METHODS: This study utilizes F3, lutein, β-sitosterol, and stigmasterol to be administered in MDA-MB-231 cells for measurement of antiglycolytic activities through cell poliferation, glucose uptake, and lactate concentration assays. Cell proliferation was assessed by MTT assay of MDA-MB-231 cells after treatment with F3 and its bioactive components lutein, β-sitosterol, and stigmasterol. The IC50 value in each compound was determined by MTT assay to be used in subsequent assays. The determination of glucose uptake activity and lactate concentration were quantified using fluorescence spectrophotometry.
RESULTS: Antiproliferative activities were observed for F3 and its bioactive components, with IC50 values of 100 µg/mL (F3), 20 µM (lutein), 25 µM (β-sitosterol), and 90 μM (stigmasterol) in MDA-MB-231 cells at 48 h. The percentage of glucose uptake and lactate concentration in MDA-MB-231 cells treated with F3, lutein, or β sitosterol were significantly lower than those observed in the untreated cells in a time-dependent manner. However, treatment with stigmasterol decreased the concentration of lactate without affecting the glucose uptake in MDA-MB-231 cells.
CONCLUSION: The antiglycolytic activities of F3 on MDA-MB-231 cells are attributed to its bioactive components.
Fulltext Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells

Nik Mohamed Kamal NNS, Abdul Aziz FA, Tan WN, Fauzi AN, Lim V

Molecules, 2021 Jun 09;26(12).
PMID: 34207699 DOI: 10.3390/molecules26123518

Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
Fulltext Green Biosynthesis, Antioxidant, Antibacterial, and Anticancer Activities of Silver Nanoparticles of Luffa acutangula Leaf Extract

Nallappan D, Fauzi AN, Krishna BS, Kumar BP, Reddy AVK, Syed T, et al.

Biomed Res Int, 2021;2021:5125681.
PMID: 34631882 DOI: 10.1155/2021/5125681

Studies on green biosynthesis of newly engineered nanoparticles for their prominent medicinal applications are being the torch-bearing concerns of the state-of-the-art research strategies. In this concern, we have engineered the biosynthesized Luffa acutangula silver nanoparticles of flavonoid O-glycosides in the anisotropic form isolated from aqueous leave extracts of Luffa acutangula, a popular traditional and ayurvedic plant in south-east Asian countries. These were structurally confirmed by Ultraviolet-visible (UV-Vis), Fourier transform infrared spectroscopy accessed with attenuated total reflection (FTIR-ATR) spectral analyses followed by the scanning electron microscopic (SEM) and the X-ray diffraction (XRD) crystallographic studies and found them with the face-centered cubic (fcc) structure. Medicinally, we have explored their significant antioxidant (DPPH and ABTS assays), antibacterial (disc diffusion assay on E. coli, S. aureus, B. subtilis, S. fecilis, and S. boydii), and anticancer (MTT assay on MCF-7, MDA-MB-231, U87, and DBTRG cell lines) potentialities which augmented the present investigation. The molecular docking analysis of title compounds against 3NM8 (DPPH) and 1DNU (ABTS) proteins for antioxidant activity; 5FGK (Gram-Positive Bacteria) and 1AB4 (Gram-Negative Bacteria) proteins for antibacterial activity; and 4GBD (MCF-7), 5FI2 (MDA-MB-231), 1D5R (U87), and 5TIJ (DBTRG) proteins for anticancer activity has affirmed the promising ligand-protein binding interactions among the hydroxy groups of the title compounds and aspartic acid of the concerned enzymatic proteins. The binding energy varying from -9.1645 to -7.7955 for Cosmosioside (1, Apigenin-7-glucoside) and from -9.2690 to -7.8306 for Cynaroside (2, Luteolin-7-glucoside) implies the isolated compounds as potential bioactive compounds. In addition, the performed studies like QSAR, ADMET, bioactivity properties, drug scores, and toxicity risks confirmed them as potential drug candidates and aspartic acid receptor antagonists. This research auxiliary augmented the existing array of phytological nanomedicines with new drug candidates that are credible with multiple bioactivities.