In embryonic development and throughout life, there are some cells, which can exhibit phenotypic plasticity. Phenotypic plasticity is the ability of cells to differentiate into multiple lineages. In normal development, plasticity is highly regulated whereas cancer cells reactivate this dynamic ability for their own progression. The re-activation of these mechanisms enables cancer cells to acquire a cancer stem cell (CSC) phenotype-a subpopulation of cells with the increased ability to survive in a hostile environment and resist therapeutic insults. There are several contributors, which fuel CSC plasticity in different stages of disease progression such as a complex network of tumour stroma, epidermal microenvironment and different sub-compartments within tumour. These factors play a key role in the transformation of tumour cells from a stable condition to a progressive state. In addition, flexibility in the metabolic state of CSCs helps in disease progression. Moreover, epigenetic changes such as chromatin remodeling, DNA methylation could stimulate the phenotypic change of CSCs. Development of resistance to therapy due to highly plastic behaviours of CSCs is a major cause of treatment failure in cancers. However, recent studies explored that plasticity can also expose the weaknesses in CSCs, thereby could be utilized for future therapeutic development. Therefore, in this review, we discuss how cancer cells acquire the plasticity, especially the role of the normal developmental process, tumour microenvironment, and epigenetic changes in the development of plasticity. We further highlight the therapeutic resistance property of CSCs attributed by plasticity. Also, outline some potential therapeutic options against plasticity of CSCs.

A lectin (termed NNTL) was purified from the extracts of Nymphaea nouchali tuber followed by anion-exchange chromatography on DEAE-cellulose, hydrophobic chromatography on HiTrap Phenyl HP and by repeated anion-exchange chromatography on HiTrap Q FF column. The molecular mass of the purified lectin was 27.0 ± 1.0 kDa, as estimated by SDS/PAGE both in the presence and in the absence of 2-mercaptoethanol. NNTL was an o-nitrophenyl β-D-galactopyranoside sugar-specific lectin that agglutinated rat, chicken and different groups of human blood cells and exhibited high agglutination activity over the pH range 5-9 and temperatures of 30-60 °C. The N-terminal sequence of NNTL did not show sequence similarity with any other lectin and the amino acid analysis revealed that NNTL was rich in leucine, methionine and glycine residues. NNTL was a glycoprotein containing 8% neutral sugar and showed toxicity against brine shrimp nauplii with an LC(50) value of 120 ± 29 μg/ml and exerted strong agglutination activity against four pathogenic bacteria (Bacillus subtilis, Sarcina lutea, Shigella shiga and Shigella sonnei). In addition, antiproliferative activity of this lectin against EAC (Ehrlich ascites carcinoma) cells showed 56% and 76% inhibition in vivo in mice at 1.5 and 3 mg·kg(-1)·day(-1) respectively. NNTL was a divalent ion-dependent glycoprotein, which lost its activity markedly in the presence of denaturants. Furthermore, measurement of fluorescence spectra in the presence and absence of urea and CaCl(2) indicated the requirement of Ca(2+) for the stability of NNTL.

Background: Cancer Stem Cells (CSCs) are the subpopulation of cancer cells which are directly involved in drug resistance, metastases to distant organ and cancer recurrence. Methods: A systematic literature search was conducted through various electronic databases including, Pubmed, Scopus, Google scholar using the keywords "cancer stem cells" and "natural compounds" in the present study. Articles published between 1999 and 2019 were reviewed. All the expositions concerning CSCs associated cancer pathogenesis and therapy resistance, as well as targeting these properties of CSCs by natural compounds were selected for the current study. Results: Natural compounds have always been thought as a rich source of biologically active principles, which target aberrantly activated signaling pathways and other modalities of CSCs, while tethering painful side effects commonly involved in the first-line and second-line chemo-radiotherapies. In this review, we have described the key signaling pathways activated in CSCs to maintain their survival and highlighted how natural compounds interrupt these signaling pathways to minimize therapy resistance, pathogenesis and cancer recurrence properties of CSCs, thereby providing useful strategies to treat cancer or aid in cancer therapy improvement. Like normal stem cells, CSCs rely on different signaling pathways and other properties for their maintenance. Therefore, the success of cancer treatment depends on the development of proper anti-neoplastic drugs capable of intercepting those signaling pathways as well as other properties of CSCs in order to eradicate this evasive subpopulation of cancer cells. Conclusion: Compounds of natural origin might act as an outstanding source to design novel therapies against cancer stem cells.

Background: Adverse side effects of currently available therapies against cancer, leads scientists to find effective compounds from natural sources. Objective: In the present study, stem-bark of Mycelia champaca is subjected to evaluate its anti-proliferative effect against Ehrlich ascites carcinoma (EAC) cells. To date, anti-proliferative effects of M. champaca bark extract against EAC cell line has not been reported elsewhere. Therefore, we intended to investigate the anti-proliferative potential of M. champaca bark extract against EAC cells in vivo. Methods: In vivo anticancer activity was evaluated against EAC cells bearing Swiss albino mice by monitoring parameters such as tumor cell proliferation, tumor weight measurement, and survival time etc. The mechanism of EAC killing was examined by observation of cell morphology and analysis the expression of certain cancer related genes. In vitro antioxidant potentiality was determined in terms of several common antioxidant assays. In addition, total phenolic and flavonoids contents were measured to insure the presence of phytochemicals. Results: M. champaca bark extract showed strong antioxidant activities which were found to be strongly correlated (P< 0.001) with phenolics and flavonoids contents. Furthermore, it was found that bark extract decreased tumor cell proliferation (77.46%; P< 0.01), tumor weight (42.13%; P< 0.001) and increased life span of tumor bearing mice (71.97%; P< 0.01) at the dose of 250mg/kg (intraperitoneal; i.p.). M. champaca bark also altered the depleted hematological parameters such as red blood cell, white blood cell, hemoglobin (Hb%) towards normal in tumor bearing mice. In addition, upregulation ofp53, Bax and downregulation Bcl-2 followed by treatmentindicated M. champacabark could induce apoptosis of EAC cells. Conclusion: These results indicated that MEMCB possesses significant cytotoxic activities against EAC cells and has a strong in vitro antioxidant capacity. Therefore, bark of M. champaca could be considered as a potential resource of anti-cancer agents, which might be used to formulate effective anticancer drugs.