M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands

Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. The CSF1R pathway is a promising therapeutic target in many human diseases, including neurological disorders or cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands - Csf1a, Csf1b and Il34, in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors, Csf1ra and Csf1rb, however there is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Furthermore, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as both csf1rbΔ4bp and il34Δ5bp deficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors and that the expression of csf1ra and csf1rb is non-overlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.

Phytoconstituents of Lantana camara L.: Rekindling Hope in the Cancer Treatment

Background: Lantana camara L. belongs to the family Verbenaceae. It originated in Tropical America in Southern Georgia and to the North of Texas and was introduced in Calcutta, India in the year 1809 as an ornamental hedge. The plant L. Camara is also distributed in Southeast Asia, China, Australia, Brazil, West Indies, Kenya, Mexico, East Africa, Tanzania. Many of its phytoconstituents possess medicinal properties which are used traditionally to treat fever, uterine hemorrhage, and excess menstrual discharge, chronic ulcers, rheumatism, gonorrhea, toothache, gastrointestinal pain, etc, and has been used in Brazil for curing malaria, mange, headaches, colds, and fevers. Objectives: The review elaborates traditional practices, phytochemistry of Lantana camara L. along with the role of Lantana camara in various types of cancers. Method: The data on L. camara was collected through different online databases like Web of Science, PubMed, Science Direct, Springer, and Google Scholar. Results: Major phytoconstituents isolated from the plant shows anticancer activity specially lantadene A-D, icterogenin, oleanolic acid, lantacamaric acid A, B, oleanonic acid, etc. In vitro and in vivo studies demonstrate its potential for various cancers. Certain extracts, isolated compounds, and their semi-synthetic derivatives have depicted a significant cytotoxic and anti-proliferative effect. Conclusion: Clinical studies are not yet established, therefore, making it crucial to direct future researches in that area.

Anti-proliferation of Melanoma Cells and Immune Stimulation by the Cyanobacterial Indole-alkaloid Scytonemin

Under the stress of ultraviolet radiation some cyanobacteria synthesize scytonemin, a protective pigment against DNA photodamage. In addition to photoprotection, scytonemin has been shown to have an anti-proliferative effect on various types of malignant cells. In this study the effect of scytonemin on melanoma and spleen cells was assessed both in vitro using tissue cultures and in vivo in mice models. Melanoma and spleen cells were exposed to 0.08 to 10 μM of scytonemin, and cell proliferation was measured using tritiated thymidine uptake. The data suggest that scytonemin acts as an inhibitor for melanoma cells in a concentration-dependent manner while enhancing the proliferation of spleen cells, suggesting that it can potentially augment the immune response. Furthermore, mice injected with melanoma cells and scytonemin produced fewer tumors than mice that did not receive scytonemin, although the data were not significant. This study adds to the growing body of research that scytonemin may be beneficial as a future anticancer agent to prevent tumor cell growth.

Combination of cytostatic chemotherapy with cisplatin and photodynamic therapy with Radachlorin reduced resistance of K562 and Hela cell lines

In this work were study combination effect of photodynamic therapy and cisplatin on the proliferation activity of K562 human leukemia cells and Hela cervical carcinoma cells. A decrease in cell viability and an increase the fraction of apoptotic cells for combination treatment compared with single therapy were observed. It has been shown that the G2/M-phase of cell cycle decreases compared with cisplatin treatment alone, which demonstrates an increase anti-proliferative effect. The combination index of the photodynamic therapy with Radachlorin and cisplatin was calculated and indicates a synergistic effect.

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

Background Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC.

The Specific Anti-cancerous Mechanisms Suggesting Spirulina Alga as a Promising breast Cancer Fighter

Breast cancer is the most widely recognized and leading to global death incidences among women, traditional medications employ herbal sources in both prevention and dealing strategies of this lethal disease. It is well known that Patients suffering from cancer use plant derived therapy to complement or as alternatives for standard treatment .Strong anti-proliferative effects against cancer cell line by using Spirulina was explained previously by many researchers, thus, in current review authors elucidate the excite cellular mechanisms, involving with anti-proliferative effect of several constituents (phycocyanin, polysaccharides, flavonoids, resins, saponins and alkaloids) which have detected within this alga .these mechanisms include: inter action within the immune system, DNA repair, apoptosis induction as well as antioxidant property. The selection to focus on breast cancer treatment; is the widely spread of this type of cancer among Iraqi women through the last decades the current review give a possible and a promising insight of using this alga as a natural, cheap source in management of this lethal challenge.

ANTI-PROLIFERATIVE POTENTIAL OF Carica papaya LEAVES ON BREAST CANCER CELLS – MCF-7

The study's objective is to identify the phytoconstituents and determine the anti-cancer potential of Carica papaya leaves against the MCF 7 cell line. Chloroform, ethyl acetate, and methanol extracts of C. papaya leaves were prepared by cold maceration method and qualitative phytochemical analysis was performed. The anti-proliferative effect of these extracts was determined by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and apoptotic assay by acridine orange/ethidium bromide staining method on MCF 7 cells. The effect of the extracts, with different concentrations, on DNA fragmentation, was also performed on MCF 7 cells. Qualitative analysis revealed the presence of alkaloids, flavonoids, terpenoids, steroids, saponins, tannins, glycosides, phenols, anthraquinones, proteins, and carbohydrates. Chloroform, methanol, and ethyl acetate extracts of C. papaya leaves were observed with potential DPPH free radical scavenging activity with 72%, 75%, and 78% respectively. Of these extracts, the chloroform extract (72%) was found to possess a more free radical scavenging effect against DPPH and also showed a dose-dependent effect, the maximum at 100µg/ml, on DNA fragmentation in MCF 7 cells. Further, chloroform extract showed a maximum anti-proliferative effect on MCF-7 cells with IC50 at 22±1.5µg/ml, whereas methanol and ethyl acetate extract at 30±0.5 µg/ml and 28±0.5 µg/ml respectively. Increased apoptosis in MCF 7 cells was observed with an increased concentration of chloroform extract of C. papaya. From the results of this study, it can be concluded that leaf extract of C. papaya found to possess an anti-proliferative effect and antioxidant potential and it could be due to the presence of rich secondary metabolites of the plant.

A Tetravalent Biparatopic Antibody Causes Strong HER2 Internalization and Inhibits Cellular Proliferation

The overexpression of tyrosine kinase HER2 in numerous cancers, connected with fierce signaling and uncontrolled proliferation, makes it a suitable target for immunotherapy. The acquisition of resistance to currently used compounds and the multiplicity of signaling pathways involved prompted research into the discovery of novel binders as well as treatment options with multiple targeting and multispecific agents. Here we constructed an anti-HER2 tetravalent and biparatopic symmetrical IgG-like molecule by combining the Fab of pertuzumab with a HER2-specific Fcab (Fc fragment with antigen binding), which recognizes an epitope overlapping with trastuzumab. In the strongly HER2-positive cell line SK-BR-3, the molecule induced a rapid and efficient reduction in surface HER2 levels. A potent anti-proliferative effect, specific for the HER2-positive cell line, was observed in vitro, following the induction of apoptosis, and this could not be achieved with treatment with the mixture of pertuzumab and the parental Fcab. The inhibitory cytotoxic effect of our antibody as a single agent makes it a promising contribution to the armory of anti-cancer molecules directed against HER2-addicted cells.