Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients.
Recent statistics revealed that cancer is one among the main reasons for death throughout the world. Several treatments are available but still there is no cure when it is detected at late stages. One of the treatment modes for cancer is chemotherapy which utilizes anticancer drugs in order to eradicate the cancer cells by apoptosis. Apoptosis is a programmed cell death through which body maintains homeostasis or kills cancer cells by utilizing its cell machinery. Recent researches have concluded that dietary agents have a putative role in instituting apoptosis of cancer cells. Honey, one of the victuals rich in antioxidants, has a long-standing exposure to humans and its role in cancer prevention and treatment is a topic of current interest. Various researchers have been experimenting honey against different cancers and provided valuable insights about the apoptosis induced by the honey. This review will highlight the recent findings of apoptotic mechanism involved in different cancer cells. Further it also reports antitumor activity of honey in some animal models. Hence it is high-time to initiate more preclinical trials as well as clinical experiments which would further add to the knowledge of anticancer nature of honey and also endorse honey as a potential candidate in the war against cancer.
A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future.
Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.
Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.