scholarly journals In vitro cytotoxicity and in vivo efficacy of 5-fluorouracil-loaded enteric-coated PEG-cross-linked chitosan microspheres in colorectal cancer therapy in rats

Drug Delivery ◽  
2015 ◽  
Vol 23 (8) ◽  
pp. 2838-2851 ◽  
Author(s):  
Kuntal Ganguly ◽  
Anandrao R. Kulkarni ◽  
Tejraj M. Aminabhavi
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
In Vitro Cytotoxicity ◽  
In Vivo Efficacy ◽  
Chitosan Microspheres ◽  
Enteric Coated

scholarly journals New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1523 ◽  
Author(s):  
Yuanyuan Fu ◽  
Qianqian Gu ◽  
Li Luo ◽  
Jiecheng Xu ◽  
Yuping Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Screening Method ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Single Target ◽  
Anti Cancer

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

Silencing Bag-1 gene via magnetic gold nanoparticle-delivered siRNA plasmid for colorectal cancer therapy in vivo and in vitro

Tumor Biology ◽  
2016 ◽  
Vol 37 (8) ◽  
pp. 10365-10374 ◽  
Author(s):  
Wenbai Huang ◽  
Zhan’ao Liu ◽  
Guanzhou Zhou ◽  
Jianmin Ling ◽  
Ailing Tian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Gold Nanoparticle

scholarly journals A Redox-Sensitive Micelle-Like Nanoparticle Self-Assembled from Amphiphilic Adriamycin-Human Serum Albumin Conjugates for Tumor Targeted Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lin Chen ◽  
Feng Chen ◽  
Mengxin Zhao ◽  
Xiandi Zhu ◽  
Changhong Ke ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Disulfide Bond ◽  
Imaging System ◽  
In Vitro Cytotoxicity ◽  
Gastric Cancer Cells

The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.

scholarly journals Discovery of a novel ferroptosis inducer-talaroconvolutin A—killing colorectal cancer cells in vitro and in vivo

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Yong Xia ◽  
Shuzhi Liu ◽  
Changlin Li ◽  
Zhiying Ai ◽  
Wenzhi Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Drug Candidate ◽  
In Vivo Experiments ◽  
Colorectal Cancer Cells ◽  
Liver And Kidney ◽  
Cancer Suppression

AbstractFerropotsis is among the most important mechanisms of cancer suppression, which could be harnessed for cancer therapy. However, no natural small-molecule compounds with cancer inhibitory activity have been identified to date. In the present study, we reported the discovery of a novel ferroptosis inducer, talaroconvolutin A (TalaA), and the underlying molecular mechanism. We discovered that TalaA killed colorectal cancer cells in dose-dependent and time-dependent manners. Interestingly, TalaA did not induce apoptosis, but strongly triggered ferroptosis. Notably, TalaA was significantly more effective than erastin (a well-known ferroptosis inducer) in suppressing colorectal cancer cells via ferroptosis. We revealed a dual mechanism of TalaA’ action against cancer. On the one hand, TalaA considerably increased reactive oxygen species levels to a certain threshold, the exceeding of which induced ferroptosis. On the other hand, this compound downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. Furthermore, in vivo experiments in mice evidenced that TalaA effectively suppressed the growth of xenografted colorectal cancer cells without obvious liver and kidney toxicities. The findings of this study indicated that TalaA could be a new potential powerful drug candidate for colorectal cancer therapy due to its outstanding ability to kill colorectal cancer cells via ferroptosis induction.

scholarly journals In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of pyrazole-based small molecule inhibitors of Mdm2/4–p53 interaction

2015 ◽  
Vol 76 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Susan M. Christner ◽  
Dana M. Clausen ◽  
Jan H. Beumer ◽  
Robert A. Parise ◽  
Jianxia Guo ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
In Vitro Cytotoxicity ◽  
In Vivo Efficacy

scholarly journals Do Lipid-Based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5346
Author(s):  
Jian Sheng Loh ◽  
Li Kar Stella Tan ◽  
Wai Leng Lee ◽  
Long Chiau Ming ◽  
Chee Wun How ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticancer Agents ◽  
In Vitro Cytotoxicity ◽  
Clinical Translation ◽  
Toxicity Profile ◽  
Toxicity Data ◽  
In Vivo Efficacy ◽  
Broad Application

Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.

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