Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and animals as a self-protective mechanism to prevent grazing and predation. Interestingly, some insect species can take advantage of the CG's toxicity and by absorbing them, they are also protected from predation. The mechanism of action of CG's toxicity is inhibition of Na+/K+-ATPase (the sodium-potassium pump, NKA), which disrupts the ionic homeostasis leading to elevated Ca2+ concentration resulting in cell death. Thus, NKA serves as a molecular target for CGs (although it is not the only one) and even though CGs are toxic for humans and some animals, they can also be used as remedies for various diseases, such as cardiovascular ones, and possibly cancer. Although the anticancer mechanism of CGs has not been fully elucidated, yet, it is thought to be connected with the second role of NKA being a receptor that can induce several cell signaling cascades and even serve as a growth factor and, thus, inhibit cancer cell proliferation at low nontoxic concentrations. These growth inhibitory effects are often observed only in cancer cells, thereby, offering a possibility for CGs to be repositioned for cancer treatment serving not only as chemotherapeutic agents but also as immunogenic cell death triggers. Therefore, here, we report on CG's chemical structures, production optimization, and biological activity with possible use in cancer therapy, as well as, discuss their antiviral potential which was discovered quite recently. Special attention has been devoted to digitoxin, digoxin, and ouabain.

• Klíčová slova
• Na+/K+ ATPase, antiviral potential, cancer treatment, cardenolides, digitoxin, digoxin, drug repositioning, immunogenic cell death, secondary plant metabolites, toxins,
• MeSH
• cílená molekulární terapie * MeSH
• digitoxin farmakologie   toxicita   MeSH
• digoxin farmakologie   toxicita   MeSH
• lidé MeSH
• nádory farmakoterapie   MeSH
• ouabain farmakologie   toxicita   MeSH
• protinádorové látky farmakologie   toxicita   MeSH
• skot MeSH
• sodíko-draslíková ATPasa antagonisté a inhibitory   MeSH
• srdeční glykosidy biosyntéza   farmakologie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• digitoxin MeSH
• digoxin MeSH
• ouabain MeSH
• protinádorové látky MeSH
• sodíko-draslíková ATPasa MeSH
• srdeční glykosidy MeSH

Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.

• Klíčová slova
• advanced prostate cancer treatment, androgen deprivation therapy, antiandrogen therapy, cancer diagnostics, immunotherapy, multimodal therapy, photodynamic therapy, phototherapy, specific drug targeting,
• MeSH
• fototerapie MeSH
• hormonální protinádorové látky chemie   farmakologie   terapeutické užití   MeSH
• imunoterapie MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   imunologie   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hormonální protinádorové látky MeSH

Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication-cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation.

• Klíčová slova
• Na+/K+-ATPase activity modulation, anticancer activity, cardiac glycosides, combination therapy, digitoxigenin, digitoxin, digoxin, natural compounds, ouabain, sodium-potassium pump inhibitors,
• MeSH
• digitoxin chemie   terapeutické užití   MeSH
• digoxin chemie   terapeutické užití   MeSH
• glioblastom farmakoterapie   enzymologie   patologie   MeSH
• inhibitory enzymů chemie   terapeutické užití   MeSH
• izoenzymy antagonisté a inhibitory   chemie   metabolismus   MeSH
• klinické zkoušky jako téma MeSH
• konformace proteinů MeSH
• lidé MeSH
• molekulární modely MeSH
• nádory mozku farmakoterapie   enzymologie   patologie   MeSH
• nádory plic farmakoterapie   enzymologie   patologie   MeSH
• ouabain chemie   terapeutické užití   MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• protinádorové látky chemie   terapeutické užití   MeSH
• sodíko-draslíková ATPasa antagonisté a inhibitory   chemie   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• digitoxin MeSH
• digoxin MeSH
• inhibitory enzymů MeSH
• izoenzymy MeSH
• ouabain MeSH
• protinádorové látky MeSH
• sodíko-draslíková ATPasa MeSH

Taxanes, mainly paclitaxel and docetaxel, the microtubule stabilizers, have been well known for being the first-line therapy for breast cancer for more than the last thirty years. Moreover, they have been also used for the treatment of ovarian, hormone-refractory prostate, head and neck, and non-small cell lung carcinomas. Even though paclitaxel and docetaxel significantly enhance the overall survival rate of cancer patients, there are some limitations of their use, such as very poor water solubility and the occurrence of severe side effects. However, this is what pushes the research on these microtubule-stabilizing agents further and yields novel taxane derivatives with significantly improved properties. Therefore, this review article brings recent advances reported in taxane research mainly in the last two years. We focused especially on recent methods of taxane isolation, their mechanism of action, development of their novel derivatives, formulations, and improved tumor-targeted drug delivery. Since cancer cell chemoresistance can be an unsurpassable hurdle in taxane administration, a significant part of this review article has been also devoted to combination therapy of taxanes in cancer treatment. Last but not least, we summarize ongoing clinical trials on these compounds and bring a perspective of advancements in this field.

• Klíčová slova
• anticancer effect, antimitotic agents, cancer treatment, combination therapy, docetaxel, microtubule-stabilizing agents, natural products, paclitaxel, targeted drug delivery, taxanes,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics.

• Klíčová slova
• Na+/K+-ATPase inhibitors, anticancer activity, cardiac glycosides, cymarin, deglucohyrcanoside, digitoxin, hyrcanoside, natural product isolation, ouabain, secondary plant metabolites,
• Publikační typ
• časopisecké články MeSH

In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.

• Klíčová slova
• 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin, Laser trilobum cultivation, chemical synthesis, extraction, mipsagargin, optimization and scale-up, sarco/endoplasmic reticulum calcium ATPase (SERCA), sesquiterpene lactones, thapsigargin, trilobolide, trilobolide isolation from fruits,
• MeSH
• Apiaceae chemie   metabolismus   MeSH
• butyráty chemie   izolace a purifikace   MeSH
• furany chemie   izolace a purifikace   MeSH
• fytogenní protinádorové látky chemie   izolace a purifikace   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádory farmakoterapie   patologie   MeSH
• ovoce chemie   metabolismus   MeSH
• oxid uhličitý chemie   MeSH
• rostlinné extrakty chemie   MeSH
• sarkoplazmatická Ca2+-ATPáza antagonisté a inhibitory   metabolismus   MeSH
• superkritická fluidní chromatografie metody   MeSH
• techniky syntetické chemie * MeSH
• thapsigargin analogy a deriváty   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• butyráty MeSH
• furany MeSH
• fytogenní protinádorové látky MeSH
• oxid uhličitý MeSH
• rostlinné extrakty MeSH
• sarkoplazmatická Ca2+-ATPáza MeSH
• thapsigargin MeSH
• trilobolide MeSH Prohlížeč

Cancer is one of the greatest challenges of the modern medicine. Although much effort has been made in the development of novel cancer therapeutics, it still remains one of the most common causes of human death in the world, mainly in low and middle-income countries. According to the World Health Organization (WHO), cancer treatment services are not available in more then 70% of low-income countries (90% of high-income countries have them available), and also approximately 70% of cancer deaths are reported in low-income countries. Various approaches on how to combat cancer diseases have since been described, targeting cell division being among them. The so-called mitotic poisons are one of the cornerstones in cancer therapies. The idea that cancer cells usually divide almost uncontrolled and far more rapidly than normal cells have led us to think about such compounds that would take advantage of this difference and target the division of such cells. Many groups of such compounds with different modes of action have been reported so far. In this review article, the main approaches on how to target cancer cell mitosis are described, involving microtubule inhibition, targeting aurora and polo-like kinases and kinesins inhibition. The main representatives of all groups of compounds are discussed and attention has also been paid to the presence and future of the clinical use of these compounds as well as their novel derivatives, reviewing the finished and ongoing clinical trials.

• Klíčová slova
• Taxol, cancer treatment, clinical trials, colchicine, cytotoxicity, docetaxel, mitotic poisons, paclitaxel,
• MeSH
• docetaxel chemie   farmakologie   MeSH
• kolchicin chemie   farmakologie   MeSH
• lidé MeSH
• mitóza účinky léků   MeSH
• paclitaxel chemie   farmakologie   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• docetaxel MeSH
• kolchicin MeSH
• paclitaxel MeSH
• protinádorové látky MeSH