scholarly journals Cancer cells have distinct electrical properties that predict a susceptibility to lipophilic anions; a new cancer drug paradigm

2015 ◽  
Author(s):  
Michael D. Forrest

ABSTRACTI use the Nernst equation, parameterised with experimental data, to predict that cancer cells will accumulate more of a lipophilic anion than normal cells. This effect is correlated to charge number. Model cancer cells accumulate *100 more of an anion, *103 more di-anion, *106 more tri-anion, *108 more tetra-anion and *1010 more penta-anion (>>1 billion times more). The trend endures, conveying even greater specificity, for higher charge numbers. This effect could be leveraged for cancer therapy. Wherein the lipophilic anion is a toxin that targets some vital cellular process, which normal and cancer cells may even share. It delivers a high, lethal dose to cancer cells but a low, safe dose to normal cells. This mathematical finding conveys the prospect of a broad, powerful new front against cancer.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinliang Gao ◽  
Tao Luo ◽  
Jinke Wang

AbstractAlthough some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.


2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Teresa L. Wargasetia

MicroRNAs (miRNAs) are involved in the signaling circuits regulation within a cell andtheir deregulation plays an important role in cancer development and progression. In thisreview, we discussed miRNA biogenesis, miRNA function and the effect of miRNA abnormalitiesin cellular pathways that led to transformation of normal cells into cancer cells, as well as theindication of miRNAs as diagnostic and prognostic biomarkers of various types of cancer, asbiomarkers to predict the response to cancer therapy and the potential for development ofmiRNAs as cancer targeted therapy.Keywords: miRNA, cancer, diagnostic biomarker, prognostic biomarker, cancer therapy


Author(s):  
Wenxing Song ◽  
Xing Su ◽  
David Gregory ◽  
Wei Li ◽  
Zhiqiang Cai ◽  
...  

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.


Author(s):  
Anne-Marie Sapse

Cancer is an extraordinarily complicated group of diseases which are characterized by the loss of normal control of the maintenance of cellular organization in the tissues. It is still not completely understood how much of the disease is of genetic, viral, or environmental origin. The result, however, is that cancer cells possess growth advantages over normal cells, a reality which damages the host by local pressure effects, destruction of tissues, and secondary systemic effects. As such, a goal of cancer therapy is the destruction of cancer cells via chemotherapeutic agents or radiation. Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that post-surgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. The rationale for using chemotherapy is the control of tumor-cell populations via a killing mechanism. The major problem in this approach is the lack of selectivity of chemotherapeutic agents. Some agents indeed preferentially kill cancer cells, but no agents have been synthesized yet which kill only cancer cells and do not affect normal cells. Unfortunately, normal tissues are affected, giving rise to a multitude of side effects. In addition to drugs exhibiting cytotoxic activity, antiproliferative drugs are also formulated. According to their mode of action, anti-cancer drugs are divided into several classes. . . . alkylating agents antimetabolites DNA intercalators mitotic inhibitors lexitropsins drugs which bind covalently to DNA . . . Experimental studies of these molecules are complemented and enhanced by theoretical studies. Some of the theoretical studies use molecular mechanics methods while others apply ab initio or semi-empirical quantum-chemistry methods. Most of these molecules are large and besides their structures and properties it is important to investigate their interaction with DNA fragments (themselves large molecules). Ab initio calculations cannot always be applied to the whole system. Therefore, models are used and through a judicious choice of the entities investigated, the calculations can shed light on the problem and provide enough information to complement the experimental studies.


2020 ◽  
Vol 12 (15) ◽  
pp. 17276-17289
Author(s):  
Joanna Pilch ◽  
Edyta Matysiak-Brynda ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Zofia Mazerska ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6684
Author(s):  
Samuele Lodovichi ◽  
Tiziana Cervelli ◽  
Achille Pellicioli ◽  
Alvaro Galli

Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.


2012 ◽  
Vol 65 (1) ◽  
pp. 5 ◽  
Author(s):  
Jagat R. Kanwar ◽  
Rupinder K. Kanwar ◽  
Ganesh Mahidhara ◽  
Chun Hei Antonio Cheung

Curing cancer is the greatest challenge for modern medicine and finding ways to minimize the adverse effects caused by chemotherapeutic agents is of importance in improving patient’s physical conditions. Traditionally, chemotherapy can induce various adverse effects, and these effects are mostly caused by the non-target specific properties of the chemotherapeutic compounds. Recently, the use of nanoparticles has been found to be capable of minimizing these drug-induced adverse effects in animals and in patients during cancer treatment. The use of nanoparticles allows various chemotherapeutic drugs to be targeted to cancer cells with lower dosages. In addition to this, the use of nanoparticles also allows various drugs to be administered to the subjects by an oral route. Here, locked nucleic acid (LNA)-modified epithelial cell adhesion molecules (EpCAM), aptamers (RNA nucleotide), and nucleolin (DNA nucleotide) aptamers have been developed and conjugated on anti-cancer drug-loaded nanocarriers for specific delivery to cancer cells and spare normal cells. Significant amounts of the drug loaded nanocarriers (92 ± 6 %) were found to distribute to the cancer cells at the tumour site and more interestingly, normal cells were unaffected in vitro and in vivo. In this review, the benefits of using nanoparticle-coated drugs in various cancer treatments are discussed. Various nanoparticles that have been tried in improving the target specificity and potency of chemotherapeutic compounds are also described.


Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769222 ◽  
Author(s):  
Hossein Allahyari ◽  
Sahar Heidari ◽  
Mehdi Ghamgosha ◽  
Parvaneh Saffarian ◽  
Jafar Amani

Cancer is one of the main reasons of death in the most countries and in Iran. Immunotherapy quickly became one of the best methods of cancer treatment, along with chemotherapy and radiation. “Immunotoxin Therapy” is a promising way of cancer therapy that is mentioned in this field. Immunotoxins are made from a toxin attaching to an antibody target proteins present on cancer cells. The first-generation immunotoxins were made of a full-length toxin attached to whole monoclonal antibodies. But, these immunotoxins could bind to normal cells. DAB389IL2 was the first immunotoxin approved by the Food and Drug Administration. Current trends and researches are ongoing on finding proteins that in combination with immunotoxins have minimal immunogenicity and the most potency for target cell killing.


2020 ◽  
Vol 18 ◽  
Author(s):  
Mahdieh Ganji ◽  
Fariba Dashtestani ◽  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Fatemeh Hakimian ◽  
...  

: An anticancer drug, cisplatin (CDDP) conjugated gold nanoparticles (GNPs) via L-Lysine (Lys) linker exhibiting a significant toxicity against cancer cells. The produced nanodrug (GNPs-Lys-CDDP) was charachterized by UV-Vis spectroscopy, dynamic light scattering (DLS), Zeta potentials and electron force microscopy. The cytotoxic efficacy of the GNPs-Lys-CDDP against human breast cancer cells (SKBR3) and normal cells (MCF-10A) was evaluatedby MTT assay. Cell apoptosis and morphology changes were assessed by flowcytometery and acridine orange/ethidium bromide (AO/EtBr) staining, respectively. It was found that the GNPs-Lys-CDDP with a size of 85 nm and negatively charged with a zeta-potential of about −25 mV could be taken up by tumor cells. A marked change in the UV spectrum of GNPs-LysCDDP compare to GNPs showed a strong absorption shift in the 525 nm region. The LD50 of GNPs-Lys-CDDP against SKBR3 (1 µg.ml-1), was found to be 8 times lower than that of naked CDDP against SKBR3 (8 µg.ml-1). The nanocomplex GNPs-Lys-CDDP also significantly increased the apoptosis of SKBR3 with the lowest cytotoxic effects on normal cells. This work indicates that GNPs effectively could decrease the lethal dose of CDDP to 87%. Hence, GNPs modified by Lys, could be a good nano-carrier for chemotherapeutic drugs.


Nanomaterials ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 907 ◽  
Author(s):  
Wenxing Song ◽  
Xing Su ◽  
David Gregory ◽  
Wei Li ◽  
Zhiqiang Cai ◽  
...  

Curcumin is a promising anti-cancer drug, but its applications in cancer therapy are limited, due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate/chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to Human Caucasian Breast Adenocarcinoma cells (MDA-MB-231). Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The nanoparticle size ranged from 120–200 nm, within the optimum range for drug delivery. Controllable and sustained release of curcumin was obtained by altering the number of chitosan and alginate layers on the nanoparticles. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of a magnetic field was achieved. The fluorescence-activated cell sorting (FACS) assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3–6 fold uptake efficiency to those treated with free curcumin. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity towards MDA-MB-231 cells than HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells, as well as directed targeting make MACPs promising candidates for cancer therapy.


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