Combinatorial Delivery of Gallium (III) Nitrate and Curcumin Complex-Loaded Hollow Mesoporous Silica Nanoparticles for Breast Cancer Treatment.

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body's circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3ß(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.

Induction of ROS-dependent mitochondria-mediated intrinsic apoptosis in MDA-MB-231 cells by glycoprotein from Codium decorticatum.

Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC50 values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 µg/mL (IC25), 55 ± 0.32 µg/mL (IC50), and 30 ± 0.43 µg/mL (IC75) and 90 ± 0.57 µg/mL (IC25), 80 ± 0.48 µg/mL (IC50), and 60 ± 0.26 µg/mL (IC75), respectively. Chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨ(m)), bax/bcl-2 dysregulation, cytochrome c release, and activation of caspases 3 and 9. Apoptosis-associated factors such as reactive oxygen species (ROS) formation and loss of ΔΨ(m) were evaluated by DCFH-DA staining and flow cytometry, respectively. Cell cycle arrest of G2/M phase and expression of apoptosis associated proteins were determined using flow cytometry and Western blotting, respectively.

Stabilization of mitochondrial and microsomal function of fucoidan from Sargassum plagiophyllum in diethylnitrosamine induced hepatocarcinogenesis.

Crude fucoidan from Sargassum plagiophyllum extracted from blade and purified by Q-Sepharose fast flow anion-exchange chromatography and three fucoidan fractions were obtained. Maximum sulphate containing fucoidan fraction was considered as purified fucoidan and purity was checked with agarose gel electrophoresis. The monosaccharides of purified fucoidan analysed by HPLC revealed the presence of the sugars such as fucose as a major sugar were 70.8 mol%. The percentages of other sugars were galactose (13.5%), xylose (2.5%) and mannose (11.2%). GPC was used to analyse molecular weight of purified fucoidan and it was found to be 35 kDa. The levels of ICDH, SDH, MDH, a-KGDH, Phase-I biotransformation enzymes, and Phase-II biotransformation enzymes were decreased in cancer bearing animals which may be due to oxidative stress and mitochondrial damage and fucoidan restored these enzyme activities. The inhibition of carcinogen metabolic activation indicates the anticancer activity of fucoidan in DEN induced liver cancer.