Genoprotective potential of Macaranga species phytochemical compounds on HT-29 human colorectal adenocarcinoma cell line.

BACKGROUND: The species of genus Macaranga are widely found in Malaysian secondary forests and has been used as an alternative for treating varieties of illness. Studies have shown that the medicinal properties of this genus contain anti-inflammatory, antioxidant, and anti-cancer effects. This study aimed to determine the cytotoxicity of six isolated phytochemicals from Macaranga heynei (M. heynei), Macaranga lowii and Shorea leprosula on HT-29 human colorectal adenocarcinoma cell lines. RESULTS: One out of six isolated phytochemical compounds, identified as "Laevifolin A", showed a cytotoxicity with an IC50 value of 21.2 µM following 48 h treatment as detected using Sulforhodamine B (SRB) assay. Additionally, no induction of apoptosis and oxidative stress were observed on Laevifolin A treated HT-29 cells as determined using Annexin V-FITC/PI assay and dihydroethidine (HE) staining, respectively. Additionally, no damage to the DNA were observed as measured using the Alkaline Comet assay. Further investigation on menadione-induced oxidative DNA damage showed the genoprotective potential of Laevifolin A on HT-29 cells. CONCLUSIONS: In conclusion, this study indicated that only one compound (Laevifolin A) that extracted from M. heynei has the cytotoxicity potential to be developed as an anticancer agent in human colorectal adenocarcinoma. However, besides exhibiting cytotoxic effect, the compound also exhibits genoprotective capability that warrant further investigation.

A Cell-Based Systematic Review on the Role of Annexin A1 in Triple-Negative Breast Cancers.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-ß signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.

Toxicity of curcumin nanoparticles towards alveolar macrophage: Effects of surface charges.

Curcumin has been used for chronic lung diseases management due to its diversified molecular actions. However, the potential cytotoxicity which occurs in cells following the exposure to high concentrations of curcumin has been overlooked. This study evaluated the toxic events of curcumin nanoparticles (Cur-NPs) with alterable surface polarity in alveolar macrophages (NR8383). We aimed to establish the correlation between the toxicity of Cur-NPs with different surface charges and the internalization mechanisms of the NPs. Toxicity data showed that positively charged Cur-NPs (IC50: 9.77 ± 0.5 µg/mL) was the most potent against NR8383, followed by negatively charged Cur-NPs (IC50:13.33 ± 0.9 µg/mL) and neutral Cur-NPs (IC50:18.68 ± 1.2 µg/mL). Results from mitochondrial membrane potential, ATP content and intracellular ROS in NR8383 showed similar ranking to the toxicity assay. The predominant uptake pathway for positively and negatively charged Cur-NPs was via clathrin-mediated endocytosis, while neutral Cur-NPs was internalized via phagocytosis, micropinocytosis and clathrin-mediated endocytosis. Positively charged Cur-NPs mediates the cytotoxicity of NR8383 via lysosomal and mitochondrial-associated destabilization upon entry. In conclusion, the cytotoxicity of Cur-NPs on NR8383 is surface-charge dependent, which in turn is associated to the uptake pathway and localization of Cur-NPs in cells.

Antimutagenic, Cytoprotective and Antioxidant Properties of Ficus deltoidea Aqueous Extract In Vitro.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

In vitro toxicological assessment of gadolinium (III) chloride in V79-4 fibroblasts.

BACKGROUND: Rare earth minerals of the lanthanide series are widely used in the field of medical and clinical application. Gadolinium (Gd), the most preferred rare earth mineral is frequently used as magnets, superconductors and magnetic resonance imaging (MRI) contrast agent. Increasing production of gadolinium waste, known potent toxicity of this element and lack of information on its Material Safety Data Sheet (MSDS) prompts health risk assessment on gadolinium. In this study, cytotoxicity and genotoxicity of Gadolinium (III) chloride (GdCl3) were investigated using MTT assay, Alkaline Comet assay and Micronucleus assay, respectively. RESULTS: Our results demonstrated that the viability of GdCl3 treated V79-4 cells was significantly (p < 0.05) reduced at 1.0 mM after 24 h of incubation. However, no IC50 values were obtained. GdCl3 showed no significant (p > 0.05) DNA damage both in the presence and absence of metabolic activation. However, it induced significant (p < 0.05) clastogenic effect in V79-4 cells at 1.0 mM in the absence of metabolic activation. The clastogenic effect was also seen in the presence of metabolic activation at 0.25 mM, 0.5 mM and 1.0 mM. CONCLUSION: Taken together, our study indicated that GdCl3 had no cytotoxic effect and does not induce DNA damage. However, this study supports that GdCl3 is a probable clastogen. Further studies are needed to investigate the effect of free gadolinium ion (Gd3+) for risk assessment on human health.

Mutagenic and clastogenic characterization of poststerilized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer biosynthesized by Delftia acidovorans.

Polyhydroxyalkanoates (PHA) are naturally occurring biopolyesters that have great potential in the medical field. However, the leachables resulting from sterilization process of the biomaterials may exert toxic effect including genetic damage. Here, we demonstrate that although gamma-irradiation of poly(3-hydroxybutyrate-co-50 mol % 4-hydroxybutyrate) [P(3HB-co-4HB)] did not cause any change in the morphology by scanning electron microscopy, there was a significant degradation of this copolymer where the molecular weight was reduced by 37% after sterilization indicating the generation of leachables. Therefore, further investigation on the ability of the extract of this poststerilized copolymer to induce mutagenic effect was performed using Ames test (S. typhimurium strains TA1535 and TA1537) and umu test (S. typhimurium strain TA1535/pSK1002). Additionally, the capability of the extract to induce clastogenic effect was determined using Chinese hamster lung V79 fibroblast cells. Our results showed that with and without the presence of S9 metabolic activation, no mutagenic effects were observed in both Ames and umu tests when treated with P(3HB-co-4HB) extract. Similarly, treatment of P(3HB-co-4HB) extract in V79 fibroblast cells showed no significant production of micronuclei when compared with the positive control (Mitomycin C). Together, these results indicate that leachables of poststerilized P(3HB-co-4HB) cause no mutagenic and clastogenic effects.

In vitro biocompatibility evaluation of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer in fibroblast cells.

Among the various biomaterials available for tissue engineering and therapeutic applications, microbial polyhydroxyalkanoates offer the most diverse range of thermal and mechanical properties. In this study, the biocompatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB); containing 50 mol % of 4-hydroxybutyrate] copolymer produced by Delftia acidovorans was evaluated. The cytotoxicity, mode of cell death, and genotoxicity of P(3HB-co-4HB) extract against V79 and L929 fibroblast cells were assessed using MTT assay, acridine orange/propidium iodide staining, and alkaline comet assay, respectively. Our results demonstrate that P(3HB-co-4HB) treated on both cell lines were comparable with clinically-used Polyglactin 910, where more than 60% of viable cells were observed following 72-h treatment at 200 mg/mL. Further morphological investigation on the mode of cell death showed an increase in apoptotic cells in a time-dependent manner in both cell lines. On the other hand, P(3HB-co-4HB) at 200 mg/mL showed no genotoxic effects as determined by alkaline comet assay following 72-h treatment. In conclusion, our study indicated that P(3HB-co-4HB) compounds showed good biocompatibility in fibroblast cells suggesting that it has potential to be used for future medical applications.