cytotoxic effects
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2022 ◽  
Vol 11 ◽  
Author(s):  
Alejandra Wu Chuang ◽  
Oliver Kepp ◽  
Guido Kroemer ◽  
Lucillia Bezu

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.


Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 58
Author(s):  
Jonas Krämer ◽  
Tim Lüddecke ◽  
Michael Marner ◽  
Elena Maiworm ◽  
Johanna Eichberg ◽  
...  

Linear cationic venom peptides are antimicrobial peptides (AMPs) that exert their effects by damaging cell membranes. These peptides can be highly specific, and for some, a significant therapeutic value was proposed, in particular for treatment of bacterial infections. A prolific source of novel AMPs are arthropod venoms, especially those of hitherto neglected groups such as pseudoscorpions. In this study, we describe for the first time pharmacological effects of AMPs discovered in pseudoscorpion venom. We examined the antimicrobial, cytotoxic, and insecticidal activity of full-length Checacin1, a major component of the Chelifer cancroides venom, and three truncated forms of this peptide. The antimicrobial tests revealed a potent inhibitory activity of Checacin1 against several bacteria and fungi, including methicillin resistant Staphylococcus aureus (MRSA) and even Gram-negative pathogens. All peptides reduced survival rates of aphids, with Checacin1 and the C-terminally truncated Checacin11−21 exhibiting effects comparable to Spinosad, a commercially used pesticide. Cytotoxic effects on mammalian cells were observed mainly for the full-length Checacin1. All tested peptides might be potential candidates for developing lead structures for aphid pest treatment. However, as these peptides were not yet tested on other insects, aphid specificity has not been proven. The N- and C-terminal fragments of Checacin1 are less potent against aphids but exhibit no cytotoxicity on mammalian cells at the tested concentration of 100 µM.


2022 ◽  
Vol 11 ◽  
Author(s):  
Xinyu Mei ◽  
Huan Li ◽  
Xinpeng Zhou ◽  
Min Cheng ◽  
Kele Cui

Malignant digestive tract tumors are a great threat to human public health. In addition to surgery, immunotherapy brings hope for the treatment of these tumors. Tissue-resident memory CD8+ T (Trm) cells are a focus of tumor immunology research and treatment due to their powerful cytotoxic effects, ability to directly kill epithelial-derived tumor cells, and overall impact on maintaining mucosal homeostasis and antitumor function in the digestive tract. They are a group of noncirculating immune cells expressing adhesion and migration molecules such as CD69, CD103, and CD49a that primarily reside on the barrier epithelium of nonlymphoid organs and respond rapidly to both viral and bacterial infection and tumorigenesis. This review highlights new research exploring the role of CD8+ Trm cells in a variety of digestive tract malignant tumors, including esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. A summary of CD8+ Trm cell phenotypes and characteristics, tissue distribution, and antitumor functions in different tumor environments is provided, illustrating how these cells may be used in immunotherapies against digestive tract tumors.


Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 194
Author(s):  
Ciprian Nicolae Pilut ◽  
Aniko Manea ◽  
Ioana Macasoi ◽  
Amadeus Dobrescu ◽  
Doina Georgescu ◽  
...  

In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenzhong Chen ◽  
Seokgyu Han ◽  
Arleen Sanny ◽  
Dorothy Leung-Kwan Chan ◽  
Danny van Noort ◽  
...  

Abstract Background Most high-throughput screening (HTS) systems studying the cytotoxic effect of chimeric antigen receptor (CAR) T cells on tumor cells rely on two-dimensional cell culture that does not recapitulate the tumor microenvironment (TME). Tumor spheroids, however, can recapitulate the TME and have been used for cytotoxicity assays of CAR T cells. But a major obstacle to the use of tumor spheroids for cytotoxicity assays is the difficulty in separating unbound CAR T and dead tumor cells from spheroids. Here, we present a three-dimensional hanging spheroid plate (3DHSP), which facilitates the formation of spheroids and the separation of unbound and dead cells from spheroids during cytotoxicity assays. Results The 3DHSP is a 24-well plate, with each well composed of a hanging dripper, spheroid wells, and waste wells. In the dripper, a tumor spheroid was formed and mixed with CAR T cells. In the 3DHSP, droplets containing the spheroids were deposited into the spheroid separation well, where unbound and dead T and tumor cells were separated from the spheroid through a gap into the waste well by tilting the 3DHSP by more than 20°. Human epidermal growth factor receptor 2 (HER2)-positive tumor cells (BT474 and SKOV3) formed spheroids of approximately 300–350 μm in diameter after 2 days in the 3DHSP. The cytotoxic effects of T cells engineered to express CAR recognizing HER2 (HER2-CAR T cells) on these spheroids were directly measured by optical imaging, without the use of live/dead fluorescent staining of the cells. Our results suggest that the 3DHSP could be incorporated into a HTS system to screen for CARs that enable T cells to kill spheroids formed from a specific tumor type with high efficacy or for spheroids consisting of tumor types that can be killed efficiently by T cells bearing a specific CAR. Conclusions The results suggest that the 3DHSP could be incorporated into a HTS system for the cytotoxic effects of CAR T cells on tumor spheroids. Graphical Abstract


2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Sasadhar Majhi

Abstract Cancer is the uncontrolled growth and development of abnormal cells which is a major cause of death in both advanced and emerging countries. Although currently chemotherapy is most broadly used among an extensive range of anti-cancer therapies, it includes many demerits, such as highly toxic, side-effects, expensive and partial lack of targeting specificity. So the design and synthesis of new molecules that perform specifically on target proteins in tumor cells is a focus of contemporary research. So many researchers aim for new drugs that will be more efficient, more selective, and less toxic. Because of the interesting structures and significant biological profile, naturally occurring acridines and xanthines as well as their analogues have attracted considerable interest in researchers and technologists. Natural and synthetic acridine derivatives form a significant category of heterocycles having nitrogen that is of considerable interest for organic chemists and biological communities due to their attractive anti-cancer activity. Another important class of therapeutic agents with diverse biological properties including cytotoxic effects is xanthine derivatives which are collectively called xanthines (a group of alkaloids). Among many significant molecules based on the structure of the purine, there is a group of natural xanthines, involving theobromine, caffeine, and theophylline and analogues of xanthine display anti-cancer activity. Hence the present chapter wishes to concentrate the attention on the synthesis and anti-cancer activity of acridine and xanthine-based compounds brilliantly.


2022 ◽  
pp. 088532822110589
Author(s):  
Hiroki Chigama ◽  
Hiroyasu Kanetaka ◽  
Maiko Furuya ◽  
Kotone Yokota ◽  
Masakazu Kawashita

Antibacterial materials are widely used to prevent hospital-acquired infections. In our previous report, metal (calcium, copper or zinc)-doped raw silk fabrics were shown to possess strong antibacterial activities against Escherichia coli. However, antibacterial materials may occasionally be harmful to the human body; thus, in this study, we investigated the cytotoxicities of extracts from metal-doped raw silk fabrics with respect to fibroblasts and osteoblasts indirectly. Calcium-doped raw silk fabric demonstrated cytocompatibility with fibroblasts. Contrarily, copper- and zinc-doped raw silk fabrics remarkably decreased the cell densities of fibroblasts, indicating their cytotoxic effects. This observation could be attributed to the high concentrations of the released copper or zinc ions. However, calcium-, copper- and zinc-doped raw silk fabrics did not demonstrate any cytotoxic effects on osteoblasts because a high concentration of the serum alleviated the effects of these metal ions released from the fabrics. Thus, calcium-doped raw silk fabric is a promising antibacterial material that does not induce strong cytotoxicity. This study will facilitate the design of materials that are both antibacterial and safe.


Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 37
Author(s):  
Lucas Ian Veloso Correia ◽  
Fernanda Van Petten de Vasconcelos Azevedo ◽  
Fernanda Gobbi Amorim ◽  
Sarah Natalie Cirilo Gimenes ◽  
Lorena Polloni ◽  
...  

Some species of primitive predatory ants, despite living in a colony, exercise their hunting collection strategy individually; their venom is painful, paralyzing, digestive, and lethal for their prey, yet the toxins responsible for these effects are poorly known. Ectatomma opaciventre is a previously unrecorded solitary hunting ant from the Brazilian Cerrado. To overcome this hindrance, the present study performed the in vitro enzymatic, biochemical, and biological activities of E. opaciventre to better understand the properties of this venom. Its venom showed several proteins with masses ranging from 1–116 kDa, highlighting the complexity of this venom. Compounds with high enzymatic activity were described, elucidating different enzyme classes present in the venom, with the presence of the first L-amino acid oxidase in Hymenoptera venoms being reported. Its crude venom contributes to a state of blood incoagulability, acting on primary hemostasis, inhibiting collagen-induced platelet aggregation, and operating on the fibrinolysis of loose red clots. Furthermore, the E. opaciventre venom preferentially induced cytotoxic effects on lung cancer cell lines and three different species of Leishmania. These data shed a comprehensive portrait of enzymatic components, biochemical and biological effects in vitro, opening perspectives for bio-pharmacological application of E. opaciventre venom molecules.


Plants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 134
Author(s):  
Annarli O. Rodríguez-Ferreiro ◽  
Ania Ochoa-Pacheco ◽  
Daniel Méndez-Rodriguez ◽  
Emilia Ortiz-Beatón ◽  
Oneida Font-Salmo ◽  
...  

Plectranthus neochilus Schltr. (Lamiaceae) is a plant recently introduced in Cuba. Worldwide, it is an ethnomedicinal alternative for its use against microbial infections, but the Cuban population use the extracts to treat sleep disorders. To address this apparent incongruity, four collections (from different seasonal conditions in the year) of Cuban P. neochilus cultivars were analyzed in terms of their pharmacognostic characteristics. Three extracts using fresh and dried leaves were chemically and biologically characterized. UPLC-DAD-MS/MS analysis was performed to determine their chemical composition, while a panel of nine microorganisms was used to evaluate their antimicrobial activity. Finally, cytotoxic effects of different fractions were measured in three cell lines by the resazurin viability assay. In contrast to previously reported micro and macromorphological properties of P. neochilus, the leaves from the Cuban cultivars did not present glandular trichomes, nor did they produce quantifiable levels of essential oils. Moreover, aqueous extracts used by the population revealed no significant antimicrobial activity and were not cytotoxic. The three extracts showed a similar phytochemical composition, i.e., eight flavonoids, seven abietane diterpenes, and rosmarinic acid as the major constituent, most of them reported for the first time in this species. The low yield of essential oil, the absence of glandular trichomes, compounds with a high level of oxidation, and a moderate antimicrobial activity detected were the most distinctive pharmacognostic and biological characteristics of P. neochilus grown in Cuba. These aspects could explain its non-use as an antimicrobial.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Anna Czapka ◽  
Christian Grune ◽  
Patrick Schädel ◽  
Vivien Bachmann ◽  
Karl Scheuer ◽  
...  

Abstract Background Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(d,l-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE. Results For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around − 15 to − 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen’s egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes. Conclusions Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential. Graphical Abstract


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