Selenium is a unique, essential trace element that plays an important role in the antioxidant defense and redox regulation of biological processes. We have reported that novel selenium-containing ...platinum-based anticancer molecules (EG-Se/Pt) had selective cytotoxicity toward cancer cells. Herein, we found the underlying mechanism of selective cytotoxicity to be closely related to the glutathione antioxidant defense system. Elevated reactive oxygen species (ROS) make cancer cells more vulnerable to further elevation of ROS. EG-Se/Pt can induce abnormal increases in ROS by depletion of glutathione. Consequently, the mitochondrial membrane potential collapses and cytochrome c is released, resulting in cell apoptosis. However, EG-Se/Pt analogues, such as EG-Se/Cu and EG-Se/Ni, did not exhibit glutathione depletion capacity or selective killing activity in our investigation, although they can effectively kill cancer cells. These results suggest that the glutathione antioxidant system is an effective target to enable therapeutic selectivity. The amphiphilic property of the selenium–platinum coordination molecules facilitates their assembly into nanoparticles and prolongs the circulation time of the drug in the bloodstream, which is important for in vivo drug delivery. Our in vivo anticancer study demonstrated that the tumor growth inhibition rate of EG-Se/Pt can reach 69% (p < 0.05). What is more encouraging is that EG-Se/Pt exhibited minimal side effects compared to cisplatin. This work also provides new opportunities for the development of therapeutic strategies against cancer.
Oxide nanoparticles (NPs) have attracted considerable interest owing to their unique characteristics and possible applications, including gas detection, bioanalytical sensing, catalytic, and ...biomedical. The present work was designed to explore the effect of varying amounts (2.5 %, 5 %, and 7.5 mol%) of Zn-doping on the properties and selective anticancer efficacy of In2O3 NPs. The precipitation process was applied to prepare pure In2O3 NPs and Zn-doped In2O3 NPs. XRD, TEM, SEM, EDX, XPS, UV–Vis, and PL techniques have been employed to investigate the physicochemical properties of NPs. The XRD analysis revealed that the crystallite of the In2O3 lattice was slightly changed with the addition of Zn ions. TEM and SEM images displayed that the reduction of size of In2O3 NPs was increased with increasing Zn concentrations. The composition elements and distribution of Zn dopants within In2O3 NPs were further confirmed by EDX and XPS techniques. Based on the UV–Vis study, increasing the Zn amount improved the gap energy of In2O3 NPs by shifting edge absorption peaks to lower wavelengths. Moreover, PL spectra show that the intensity of In2O3 NPs decreased with increasing the Zn amount. The biological results indicate that the Zn-doped In2O3 NPs exhibited a significant increase in cytotoxicity with Zn doping increased against MCF-7 and HCT116cells while they have excellent biocompatibility with normal human cells (HUVECs). These results suggest that these NPs hold promise as a novel therapeutic approach in cancer treatment. This study requires more research into the biological applications of Zn-doped In2O3 NPs.
We report important progress in the preparation and development of gas-responsive fluorescent materials with potential as efficient anticancer treatments and fluorescent probes for biomedical ...imaging. An environmental stimuli-responsive multifunctional material (ESMM) composed of rhodamine 6 G containing a pH-sensitive spirolactam unit and a self-complementary multiple hydrogen-bonded adenine group was successfully synthesized through a simple and efficient two-step synthetic pathway. ESMM has extremely poor water solubility, even in a weakly acidic aqueous environment, but can easily dissolve in common organic solvents. Due to the unique polar heteroaromatic structure of the adenine group that confers chemical reactivity (or responsiveness) with CO2, hydrophobic ESMM can rapidly and completely dissolve in water on simple CO2 bubbling treatment, which is followed by formation of self-assembled spherical-like nanoparticles. The resulting nanoparticles demonstrate unique spontaneous fluorescent characteristics in water and their photophysical properties, surface charge, acid-base characteristics, and self-assembled morphology can be quickly and stably switched on and off by alternating cycles of CO2 and N2 bubbling, to thus effectively manipulate their physical performance. Importantly, in vitro cell assays clearly indicated that protonation of the adenine group by CO2 remarkably enhances the anti-hemolytic properties of ESMM and results in highly potent and selective cytotoxicity against cancer cells at low doses, but not in normal cells. In contrast, pristine ESMM did not exhibit selective cytotoxic effect on normal or cancer cells. Therefore, this newly discovered CO2-responsive system may have a great potential to improve the safety and effectiveness of chemotherapeutic drugs.
Display omitted
•Multifunctional adenine-containing rhodamine 6 G (AR) was developed.•AR spontaneously self-assembles into nanoparticles on CO2 bubbling.•CO2-protonated AR has low hemolytic activity towards red blood cells.•CO2-treated AR exhibits highly selective cytotoxicity in cancer cells.•This new system holds potential for safer, more efficient chemotherapy.
Due to the lack of early detection methods and effective treatments, pancreatic cancer has one of the lowest five-year survival rates among all cancers. We have previously identified novel ...isoprenylated coumarin compounds that exhibit preferential cytotoxicity against pancreatic adenocarcinoma cell line PANC-1 exclusively under glucose deprivation conditions.
Using cell cytotoxicity assays, we investigated the anti-proliferative mechanism of our most potent isoprenylated coumarin compound of the series, DCM-MJ-I-21, with respect to time, against two other pancreatic cancer cell lines, BxPC-3 and Capan-2. We used western blotting to quantify the autophagic flux influenced by our compound, autophagy inducers (starvation and Rapamycin), and autophagy inhibitors (chloroquine and wortmannin).
We observed a clear dependence on glucose in DCM-MJ-I-21 in BxPC-3 and Capan-2 pancreatic cancer cell lines, suggesting that our compound targets a pathway shared by these cancer cell lines when glycolysis is not an option for survival. Our lead compound increased the conversion of LC3-I to LC3-II in PANC-1, similar to the effect of chloroquine, an autophagy inhibitor. In addition, Spautin-1, another autophagy inhibitor, showed almost the same anti-proliferative activities at the same concentration under nutrient-deprived conditions as our lead compound in both 2D and 3D cell cultures.
Our lead isoprenylated coumarin compound induces selective pancreatic cancer cell death under nutrient-deprived conditions through inhibition of autophagy, potentially providing insights into new therapeutic options.
The study was aimed at the identification of a potential anti-cancer compound from the leaf extract of
, against pancreatic cancer cells (PANC-1). Out of different extracts tested, methanolic extract ...showed significant cytotoxicity at an IC
of 289.5 ± 0.03 µg/mL after 24 h (MTT assay). The safety of the extract was ascertained using normal pancreatic cells (hTERT-HPNE). Methanolic extract was able to induce apoptosis in 28.9 ± 0.01% of PANC-1 cells as determined by flow cytometry. RT-PCR analysis of PANC-1 cells also recorded an increase in the mRNA expression of pro-apoptotic genes i.e.,
(12.82 folds),
(10 folds) and
(8.74 folds) after treatment. Expression of other pro-apoptotic genes such as
and
was also upregulated by 4.04 and 4.01 folds, respectively. However, the mRNA expression of anti-apoptotic genes,
,
and
was found to be downregulated. The bioactive extract was then fractionated on preparative silica gel plates into 24 bands. Out of these, band fraction 9 exhibited significant cytotoxicity (IC
219 ± 0.04 µg/mL) on the PANC-1 cells. The mass spectral (HPLC-MS) and FTIR analysis of the fraction indicated the bioactive compound to be a derivative of Diosgenin, which can be a possible candidate for cancer therapeutics in future.
The online version contains supplementary material available at 10.1007/s13205-022-03155-w.
Background
Urolithin B (UB), the antioxidant polyphenol has a protective impact on several organs against oxidative stress. However, its bioactivity is limited by its hydrophobic structure. In the ...current study, UB was encapsulated into a liposomal structure to improve its bioactivities anticancer, and antimicrobial potential.
Method
The UB nano-emulsions (UB-NE) were synthesized and characterized utilizing FESEM, DLS, FTIR, and Zeta-potential analysis. The UB-NMs’ selective toxicity was studied by conducting an MTT assay on MCF-7, PANC, AGS, and ASPC1 cells. The AO/PI analysis verified the UB-NMs’ cytotoxicity on ASPC1 cell lines and approved the MTT results. Finally, the antibacterial activity of the UB-NMs was studied on both gram-positive (
B. subtilis
,
S. aureus
) and gram-negative (
E. Coli
,
P. aeruginosa
) bacteria by conducting MIC and MBC analysis.
Result
The 68.15 nm UB-NMs did not reduce the normal HDF cells’ survival. However, they reduced the cancer cells’ (PANC and AGS cell lines) survival at high treatment concentrations (> 250 µg/mL) compared with normal HDF and cancer MCF-7 cells. Moreover, the IC
50
doses of UB-NMs for the ASPC1 and PANC cancer cells were measured at 44.87, and 221.02 µg/mL, respectively. The UB-NMs selectively exhibited apoptotic-mediated cytotoxicity on the human pancreatic tumor cell line (ASPC1) by down-regulating BCL2 and NFKB gene expression. Also, the BAX gene expression was up-regulated in the ASPC1-treated cells. Moreover, they exhibited significant anti-bactericidal activity against the
E
.
coli
(MIC = 50 µg/mL, MBC = 150 µg/mL),
P. aeruginosa
(MIC = 75 µg/mL, MBC = 275 µg/mL),
B. subtilis
(MIC = 125 µg/mL, MBC = 450 µg/mL), and
S. aureus
(MIC = 50 µg/mL, MBC = 200 µg/mL) strains.
Conclusion
The significant selective cytotoxic impact of the UB-NMs on the human pancreatic tumor cell line makes it an applicable anti-pancreatic cancer compound. Moreover, the antibacterial activity of UB-NMs has the potential to decrease bacterial-mediated pancreatic cancer. However, several bacterial strains and further cancer cell lines are required to verify the UB-NMs’ anticancer potential.
Herniarin, a simple coumarin found in chamomile leaf rosettes is known as the oxidative stress protector. In the current study, herniarin was captured into Graphene oxide nanoparticles and coated ...with chitosan poly-cationic polymer to be used as a novel bio-compatible nano-drug delivery system and investigate its antioxidant, anti-angiogenic and anti-cancer impacts on human lung A549 cancer cells.
The Chitosan-coated Herniarin-Graphene oxide nanoparticles (CHG-NPs) were designed, produced, and characterized utilizing DLS, FESEM, FTIR, and Zeta-potential analysis. The CHG-NPs’ antioxidant activity was analyzed by conducting ABTS and DPPH antioxidant assays. The CHG-NPs’ anti-angiogenic activity was analyzed by CAM assay and verified by measuring VEGF and VEGFR gene expression levels following their increased treatment doses by applying Q-PCR technique. Finally, the CHG-NPs’ cytotoxicity was studied in the human lung A549 cancer cells.
The stable (+27.11 mV) 213.6-nm CHG-NPs significantly inhibited the ABTS/DPPH free radicals and exhibited antioxidant activity. The suppressed angiogenesis process in the CAM vessels was observed by detecting the decreased length/number of the vessels. Moreover, the down-regulated VEGF and VEGFR gene expression of the CAM blood vessels following the increased CHG-NPs treatment doses verified the nanoparticles’ anti-angiogenic potential. Finally, the CHG-NPs significantly exhibited a selective cytotoxic impact on human A549 cancer cells compared with the normal HFF cell line.
The selective cytotoxicity, strong antioxidant activity, and significant anti-angiogenic property of the nano-scaled produced CHG-NPs make it an appropriate anticancer nano-drug delivery system. Therefore, the CHG-NPs have the potential to be used as a selective anti-lung cancer compound.
Oxypeucedanin (OPD) as a powerful anti-proliferative agent found in the
Angelicae dahuricae
has been used to suppress cancer cell growth. However, the hydrophobic chemical structure has limited its ...solubility and bio-accessibility. This is the first time OPD is encapsulated into a nano-liposomal structure and coated with poly-cationic chitosan polymer as the oxypeucedanin drug delivery system to evaluate its antioxidant and anti-colon cancer potential. The chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) were synthesized utilizing the thin-layer hydration method and characterized by FESEM, DLS, FTIR, and zeta potential analysis. The anti-cancer potential of COPD-NC was analyzed by measuring the cell survival rate (MTT assay) and studying the cellular death type (AO/PI staining) following the increased treatment concentrations of COPD-NC on the HT-29 colon cancer cell line. Moreover, the COPD-NCs’ apoptotic activity was verified by analyzing Cas-3 and Cas-9 gene expression profiles. Finally, the COPD-NCs’ antioxidant activity was evaluated by applying ABTS, DPPH, and FRAP antioxidant assays. The 258.26-nm COPD-NCs significantly inhibited the HT-29 colon cancer cells compared with the normal fibroblast HFF cells. The up-regulated Cas-3 and Cas-9 gene expression exhibited the COPD-NCs’ apoptotic activity. Also, the COPD-NCs’ apoptotic activity was verified by detecting the increased apoptotic bodies following the AO/PI fluorescent staining in the increased exposure doses of COPD-NCs. Ultimately, the COPD-NCs meaningfully inhibited the ABTS-DPPH radicals and exhibited an appropriate FRAP-reductive potential. The designed nanostructure for COPD-NCs significantly improved its antioxidant potential and selective cytotoxicity on human HT-29 human cancer cells, which makes them a safe selective natural drug delivery system. Therefore, the COPD-NCs can selectively induce apoptotic death in human HT-29 cancer cells and have the potential to be studied as an anti-colon cancer compound. However, further cancer and normal cell lines are required to verify their selective cytotoxicity.
Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid ...carcinoma. Non-thermal atmospheric pressure plasma which produces reactive species has recently led to an explosion of research in plasma medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to plasma. In this study, we confirmed whether this indirect plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.
Display omitted
•MnO nanoclusters are grafted with polyglycerol (PG) and conjugated with RGD peptide.•MnO-PG-RGD is taken up by U87MG cancer cells and mainly located in the lysosomes.•The released ...Mn2+ ions promote oxidative stress in U87MG cells leading to cell death.
An efficient surface engineering strategy for MnO nanoparticles was developed to attain enhanced colloidal stability, selective uptake by and toxicity to specific cancer cells. Specifically, MnO nanoclusters prepared by polyol method were grafted with polyglycerol (MnO-PG), and then conjugated with arginine-glycine-aspartate peptide (MnO-PG-RGD) through stepwise organic reactions. The physicochemical properties of the surface engineered MnO nanoclusters were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, zeta potential, transmission electron microscopy and high-resolution transmission electron microscopy. The grafted PG layer not only largely enhanced the dispersibility and colloidal stability of MnO nanoclusters in physiological media, but also effectively inhibited non-specific cellular uptake of MnO-PG. MnO-PG-RGD was selectively taken up by human glioblastoma U87MG cells overexpressing αvβ3 integrins through receptor-mediated endocytosis. The internalized MnO-PG-RGD was mainly located in the lysosomes of U87MG cells. The acidity of lysosomes accelerated Mn2+ ions releasing, which promoted intracellular oxidative stress and further led to cell damage and apoptosis. The results indicate that appropriate surface functionalization can enable MnO nanoparticles to act as a potential anticancer agent in addition to their MRI functionality.
PDF
