Combination of Goniothalamin and Sol-Gel-Derived Bioactive Glass 45S5 Enhances Growth Inhibitory Activity via Apoptosis Induction and Cell Cycle Arrest in Breast Cancer Cells MCF-7.

Background: Combination of natural products with chemically synthesised biomaterials as cancer therapy has attracted great interest lately. Hence, this study is aimed at investigating the combined effects of goniothalamin and bioactive glass 45S5 (GTN-BG) and evaluating their anticancer properties on human breast cancer cells MCF-7. Methods: The BG 45S5 was prepared using the sol-gel process followed by characterisation using PSA, BET, SEM/EDS, XRD, and FTIR. The effects of GTN-BG on the proliferation of MCF-7 were assessed by MTT, PrestoBlue, and scratch wound assays. The cell cycle analysis, Annexin-FITC assay, and activation of caspase-3/7, caspase-8, and caspase-9 assays were determined to further explore its mechanism of action. Results: The synthesised BG 45S5 was classified as a fine powder, having a rough surface, and contains mesopores of 12.6 nm. EDS analysis revealed that silica and calcium elements are the primary components of BG powders. Both crystalline and amorphous structures were detected with 73% and 27% similarity to Na2Ca2(Si2O7) and hydroxyapatite, respectively. The combination of GTN-BG was more potent than GTN in inhibiting the proliferation of MCF-7 cells. G0/G1 and G2/M phases of the cell cycle were arrested by GTN and GTN-BG. The percentage of viable cells in GTN-BG treatment was significantly lower than that in GTN. In terms of activation of initiator caspases for both extrinsic and intrinsic apoptosis pathways, caspase-8 and caspase-9 were found more effective in response to GTN-BG than GTN. Conclusion: The anticancer effect of GTN in MCF-7 cells was improved when combined with BG. The findings provide significant insight into the mechanism of GTN-BG against MCF-7 cells, which can potentially be used as a novel anticancer therapeutic approach.

Regular Kratom ( Mitragyna speciosa Korth.) Use and Its Association With Endoplasmic Reticulum Stress Response.

OBJECTIVES: This study determined the association between expression of the endoplasmic reticulum (ER) stress sensor mRNA in the peripheral leukocytes and the patterns of kratom use and evaluated the correlations between the levels of the ER stress sensor mRNA and the severity of kratom dependence and kratom induced depressive symptoms among people who use kratom (PWUK). METHODS: A total of 20 PWUK and 20 age matched non-kratom using healthy controls were recruited. Data collected from PWUK included patterns of kratom use, severity of kratom dependence, and severity of depressive symptoms during abstinence from kratom. The mRNA expression of binding immunoglobulin protein ( BiP ), X-box binding protein 1, activating transcription factor 4, and C/-EBP homologous protein ( CHOP ) (major indicators of ER stress response) were analyzed using quantitative reverse transcription polymerase chain reaction in leucocyte-derived total RNA sample of the participants. RESULTS: PWUK regardless of their pattern of kratom use recorded significantly higher expression of BiP mRNA compared with controls. Expression of CHOP mRNA was only significantly higher in those who first consumed kratom at the age of 18 years and above and those who have been using kratom for longer than 6 years, compared with controls. Higher expression of BiP , ATF4 , and CHOP mRNA were significantly positive correlated with greater severity of kratom dependence. Although only higher expression of BiP and CHOP mRNA were significantly positively correlated with greater severity of depressive symptoms. CONCLUSIONS: Regular kratom consumption may activate the ER stress pathway and there may be a link between altered ER stress response and kratom dependence and kratom induced depressive symptoms.

Lipoproteins as Markers for Monitoring Cancer Progression.

Lipoproteins are among the contributors of energy for the survival of cancer cells. Studies indicate there are complex functions and metabolism of lipoproteins in cancer. The current review is aimed at providing updates from studies related to the monitoring of lipoproteins in different types of cancer. This had led to numerous clinical and experimental studies. The review covers the major lipoproteins such as LDL cholesterol (LDL-C), oxidized low-density lipoprotein cholesterol (oxLDL-C), very low-density lipoprotein cholesterol (VLDL-C), and high-density lipoprotein cholesterol (HDL-C). This is mainly due to increasing evidence from clinical and experimental studies that relate association of lipoproteins with cancer. Generally, a significant association exists between LDL-C with carcinogenesis and high oxLDL with metastasis. This warrants further investigations to include Mendelian randomization design and to be conducted in a larger population to confirm the significance of LDL-C and its oxidized form as prognostic markers of cancer.

Formulation, Characterization and Cytotoxicity Effects of Novel Thymoquinone-PLGA-PF68 Nanoparticles.

Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone's (TQ) biological activity before reaching the target sites. Synthesis of nanoparticles was successfully completed by encapsulating TQ with polymeric poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol) and Pluronics F68 (TQ-PLGA-PF68) using an emulsion-solvent evaporation technique. The size and encapsulation efficiency of TQ-PLGA-PF68 nanoparticles were 76.92 ± 27.38 nm and 94%, respectively. TQ released from these encapsulants showed a biphasic released pattern. Cytotoxicity activity showed that tamoxifen-resistant (TamR) MCF-7 breast cancer cells required a higher concentration of TQ-PLGA-PF68 nanoparticles than the parental MCF-7 cells to achieve IC50 (p < 0.05). The other two resistant subtypes (TamR UACC732 inflammatory breast carcinoma and paclitaxel-resistant (PacR) MDA-MB 231 triple-negative breast cell line) required a lower concentration of TQ-PLGA-PF68 nanoparticles compared to their respective parental cell lines (p < 0.05). These findings suggest that TQ encapsulation with PLGA-PEG and Pluronics F68 is a promising anti-cancer agent in mitigating breast cancer resistance to chemotherapeutics. In future studies, the anti-cancer activity of TQ-PLGA-PF68 with the standard chemotherapeutic drugs used for breast cancer treatment is recommended.

Beetroot as a Potential Functional Food for Cancer Chemoprevention, a Narrative Review.

Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot's nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.

Comparative Study On Effects Of Lipoproteins On Growth And Migration Characteristics Of Tamoxifen Resistant Breast Cancer Cells

@#Introduction: Resistance towards treatment is one of the challenges in breast cancer therapy. Recent studies show the link between lipoprotein with cancer resistance and progression. Clinical data indicates that oxidized low-density lipoprotein (oxLDL) and very low-density lipoprotein (VLDL) play roles the progression of breast cancer. Therefore, purpose of this study was to determine the roles of lipoproteins on migration of breast cancer cell and compare the effects of oxLDL and VLDL. Methods: Parent MCF-7 cells were purchased from ATCC, while the Tamoxifen-resistant MCF-7 (Tam-R MCF-7) was developed by pulse treatment method. Tam-R cells were treated with gradual increase in tamoxifen concentration for 72 hours in Dulbecco’s Modified Eagle’s medium (DMEM) without phenol red. Cell viability test was done to measure the fold changes of Tam-R MCF-7 cells. Migration characteristics was studied using wound healing assay. Cells were treated with 10 μg/mL of oxLDL and VLDL up to 72 hours. Results: From the cell viability test, Tam-R MCF-7 cells had 4-fold increase of resistance than parental cells. Tam-R MCF-7 had acquired resistance to Tamoxifen and achieved a clinically relevant level of resistance. Lipoproteins were found to cause morphological changes, where cells exhibited elongation and dendritic-like growth compared to control cells. Both MCF-7 parental cells and Tam-R MCF-7 cells showed higher percentage of wound closure when treated with oxLDL. In contrast, VLDL treatment caused reduction in cell migration compared to oxLDL. Conclusion: Findings suggest that oxLDL may further promote resistant breast cancer cell migration compared to VLDL.

Assessment of gonadotropins and testosterone hormone levels in regular Mitragyna speciosa (Korth.) users.

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) also known as kratom, is a native medicinal plant of Southeast Asia with opioid-like effects. Kratom tea/juice have been traditionally used as a folk remedy and for controlling opiate withdrawal in Malaysia. Long-term opioid use is associated with depletion in testosterone levels. AIM OF THE STUDY: Since kratom is reported to deform sperm morphology and reduce sperm motility, we aimed to clinically investigate the testosterone levels following long-term kratom tea/juice use in regular kratom users. METHODS: A total of 19 regular kratom users were recruited for this cross-sectional study. A full-blood test was conducted including determination of testosterone level, follicle stimulating hormone (FSH) and luteinizing hormone (LH) profile, as well as hematological and biochemical parameters of participants. RESULTS: We found long-term kratom tea/juice consumption with a daily mitragynine dose of 76.23-94.15 mg did not impair testosterone levels, or gonadotrophins, hematological and biochemical parameters in regular kratom users. CONCLUSION: Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans.

Evaluating the hematological and clinical-chemistry parameters of kratom (Mitragyna speciosa) users in Malaysia.

ETHNOPHARMACOLOGICAL RELEVANCE: Kratom (Mitragyna speciosa Korth.) from the Rubiaceae family is an indigenous tropical medicinal tree of Southeast Asia. Kratom leaves have been used for decades in Malaysia and Thailand in traditional context for its perceived vast medicinal value, and as a mild stimulant among manual labourers. Kratom consumption has been reported to cause side-effects in kratom users. AIM OF THE STUDY: To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia. METHODS: A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users. RESULTS: Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users. CONCLUSION: These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.