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Production of Life-Saving Drugs from Marine Sources
Published in Prasenjit Mondal, Ajay K. Dalai, Sustainable Utilization of Natural Resources, 2017
Cytarabine (3) received FDA’s approval as an anticancer drug in June 1969 (Schwartsmann et al. 2003). It (also known as ara-C or 1-β-D-arabinofuranosylcytosine) received the pleasure of being the first marine-derived drug used for the management of leukemia. Inspired by arabinose nucleosides, cytarabine or cytosine arabinoside was produced artificially by R. Walwick in 1959 and natural-sourced cytarabine was isolated from the fermentation broth of Streptomyces griseus. Subsequently, cytarabine was isolated from the gorgonian Eunicella cavolini (Cimino et al. 1984). Cytarabine is sold under the trade name Cytosar-U® or Depocyt® and is prescribed mainly for the treatment of non-Hodgkin lymphoma and acute myeloid leukemia (AML; Wang et al. 1997).
The potential interaction of environmental pollutants and circadian rhythm regulations that may cause leukemia
Published in Critical Reviews in Environmental Science and Technology, 2022
Francisco Alejandro Lagunas-Rangel, Błażej Kudłak, Wen Liu, Michael J. Williams, Helgi B. Schiöth
Plasticizers, produced for nearly 100 years, have become ubiquitous in society and are found in a variety of everyday products. Many of these have been shown to participate in the development of diseases when they are introduced into the body by inhalation, ingestion and dermal absorption (Zarus et al., 2021). Some of these such as bisphenol A (BPA), phthalates and perfluorinated chemicals can act as endocrine disrupting compounds (EDCs) with significant consequences including infertility, polycystic ovary syndrome (PCOS), precocious puberty, hormone-dependent tumors, such as breast and prostate cancer, and several metabolic disorders linked to cancer (Braun et al., 2013; Dematteo et al., 2012; Diamanti-Kandarakis et al., 2009; Loganathan et al., 2019). BPA is widely used in plastics intended for direct contact with food, including plastic packaging, coatings of cans and jar caps, as well as kitchenware. BPA at nanomolar concentrations promotes the proliferation of acute promyelocytic leukemia HL-60 and histiocytic lymphoma U937 cells and reduces their sensitivity to daunorubicin and cytarabine by causing an increase in IL-4 levels through NFAT1, and increasing IL-6 levels through the NF‐κB pathway (Zhang et al., 2020). However, leukemic cells were also shown to be more sensitive to the cytotoxic effects of BPA than other types of cancer cells, with apoptosis cascades being activated more rapidly in leukemic cells (Terasaka et al., 2005). NB4 cells that possess the PML-RARA fusion protein were the most sensitive to BPA, which induced their differentiation and activated apoptosis pathways by causing an increase in the levels of p21, p27, p16 and RB, while decreasing those of cyclin D1 (Bontempo et al., 2009). Interestingly, in mouse pro-opiomelanocortin (POMC) neurons, BPA has altered the circadian clock, mainly in the BMAL1, PER2 and REV-ERBa genes, and also caused an increase in the binding of BMAL1 to its target promoters that they are reflected in deleterious effects on the expression of neuropeptides (Loganathan et al., 2019).