A GSH/CB Dual-Controlled Self-Assembled Nanomedicine for High-Efficacy Doxorubicin-Resistant Breast Cancer Therapy

Chemoresistance is a major therapeutic obstacle in the treatment of breast cancer. Therefore, how to overcome chemoresistance is a problem to be solved. Here, a glutathione (GSH)/cathepsin B (CB) dual-controlled nanomedicine formed by cyclic disulfide-bridged peptide (cyclic-1a) as a potent anticancer agent is reported. Under the sequential treatment of GSH and CB, cyclic-1a can efficiently self-assemble into nanofibers. In vitro studies show that cyclic-1a promotes the apoptosis of MCF-7/DOX cells by inducing the cleavages of caspase-3 and PARP. In vivo studies confirm that cyclic-1a significantly inhibits the progression of MCF-7/DOX cells-derived xenograft in nude mice, with no obvious adverse reactions. This study provides a paradigm of GSH/CB dual-controlled nanomedicine for high-efficacy and low-toxic DOX-resistant breast cancer therapy.

Repurposing Tranexamic Acid as an Anticancer Agent

Tranexamic Acid (TA) is a clinically used antifibrinolytic agent that acts as a Lys mimetic to block binding of Plasminogen with Plasminogen activators, preventing conversion of Plasminogen to its proteolytically activated form, Plasmin. Previous studies suggested that TA may exhibit anticancer activity by blockade of extracellular Plasmin formation. Plasmin-mediated cleavage of the CDCP1 protein may increase its oncogenic functions through several downstream pathways. Results presented herein demonstrate that TA blocks Plasmin-mediated excision of the extracellular domain of the oncoprotein CDCP1. In vitro studies indicate that TA reduces the viability of a broad array of human and murine cancer cell lines, and breast tumor growth studies demonstrate that TA reduces cancer growth in vivo. Based on the ability of TA to mimic Lys and Arg, we hypothesized that TA may perturb multiple processes that involve Lys/Arg-rich protein sequences, and that TA may alter intracellular signaling pathways in addition to blocking extracellular Plasmin production. Indeed, TA-mediated suppression of tumor cell viability is associated with multiple biochemical actions, including inhibition of protein synthesis, reduced activating phosphorylation of STAT3 and S6K1, decreased expression of the MYC oncoprotein, and suppression of Lys acetylation. Further, TA inhibited uptake of Lys and Arg by cancer cells. These findings suggest that TA or TA analogs may serve as lead compounds and inspire the production of new classes of anticancer agents that function by mimicking Lys and Arg.

Assessment cytotoxic assay of Rhizophora plants mangrove using brine shrimp (Artemia salina L) model

Rhizophoraceae is the main family of mangroves as a source of bioactive compounds originating from the coast. Ethnophamacologically Rhizophoraceae has been used in various traditional medicine. Natural sources as anticancer from the Rhizophoraceae family are interesting to know. This study aimed to determine the cytotoxic bioactivity of methanolic extracts of roots, bark, leaves, and fruit/hypocotyl from five species of Rhizophoraceae (Bruguieria cylindrica, B. gymnorrhiza, Ceriops decandra, Rhizophora apiculata, and R. mucronata) from the Langsa mangrove forest, Aceh. The method used in this study was the Brine Shrimp Lethality Test (BSLT) bioassay using Artemia salina Leach at extract concentrations of 1, 10, 100, 500, and 1000 μg/ml. Samples were extracted using the maceration method and methanol as the solvent. The cytotoxic activity of 20 Rhizophoraceae methanol extracts showed that 12 extracts were toxic with an LC50 range of 31.5 - 934.9 μg/ml (based on LC50 ≤ 1000 μg/ml). The two extracts of which the closest to highly toxic (based on LC50 ≤ 30 μg/ml) were C. decandra bark showed LC50 of 31.5 μg/ml, and R. mucronata bark showed LC50 31.8 μg/ml. This shows that Rhizophoraceae extract has potential as a natural anticancer agent. In the five rhizophoraceae species, C. decandra was the most active compared to other species. In the four plant parts, the bark was the most toxic.

In vitro antimicrobial, anticancer, and apoptosis-inducing effects of the methanolic extract of Launaea mucronata

Traditional medicine is widely used in the treatment and management of various ailments due to its low toxicity, low number of side effects and low cost. Many components of common fruits and vegetables play crucial roles as chemopreventive or chemotherapeutic agents. This study aimed to evaluate in vitro the antioxidant, cytotoxic and antimicrobial activities of Launaea mucronata’s methanolic stems and leaves extract. In this screening study, Launaea mucronata’s methanolic extracts showed remarkably antifungal activity against Candida albicans. The maximum zone of inhibition of the methanolic extract of Launaea mucronata leaves was detected against Proteus vulgaris with inhibition zones of 17.8 mm and 14.6 mm, respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay results showed high antioxidant activity for the extract almost comparable to that of ascorbic acid at 30 µg/ml, which indicates that it might potentially be developed into a successful antioxidant agent. Meanwhile, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed by screening the extract against HepG2 (Hepatocellular), A549 (Lung), HCT116 (Colon) and MCF7 (Breast) cancer cells and it was found that the extract exerted its highest activity against A549 cells with an IC50 value of 14.9 µg/ml. The extracts also shown lower cytotoxic activity against normal, healthy MRC-5 cells, with IC50 values of 204.83 g/ml for the stem extract and 412.4 g/ml for the leaves extract, respectively. This suggests that the extract is safe for normal, healthy cells, which is an important characteristic of any possible anticancer treatment. The antiproliferative and apoptosis activities of our selected plant showed that the extracts induced S-phase arrest and apoptosis in A549 cells. This high cytotoxic activity of the extract indicates that highly bioactive pure compounds could potentially be isolated from the extract in future studies and further developed into an anticancer agent specifically against lung cancer. Therefore, the current study has proven the potential of Launaea mucronata’s methanolic extract as a source of potent antioxidant and anticancer agent.