Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

We have known for a while that methylated β-cyclodextrin (MβCD) can extract cholesterol from lipid rafts and induce apoptosis in cancer cells by inhibiting activation of the PI3K-Akt-Bad pathway.

In this study from Kumamoto University (Keiichi Motoyama), MβCD with mannose (Man-MβCD) is assessed for targeting colon cancer cells expressing the mannose receptor (MR) and tumor-associated macrophages (TAM). Man-MβCD showed a significantly greater level of cellular association with colon-26 cells and M2 macrophages, and much more prominent anticancer activity than that of MβCD against MR-positive colon-26 cells. These results revealed that autophagy was the main mechanism of cell death associated with Man-MβCD. Furthermore, compared with MβCD, Man-MβCD significantly reduced tumor development following intravenous delivery to tumor-bearing mice, with no apparent side effects. Thus, Man-MβCD has the potential to be a novel anticancer drug.

If you would like to try something like this, check out this site for ideas: Custom synthesis of cyclodextrins –

Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells

More and more uses of cyclodextrin as anticancer therapy agents come to light these days. The most recent is the research of Kumamoto University (who else) showing how Folate-Appended Hydroxypropyl-β-Cyclodextrin (FA-HP-β-CyD) Induces Autophagic Cell Death in Acute Myeloid Leukemia (AML) Cells.

As reported the cytotoxic activity of FA-HP-β-CyD against AML cells was stronger than that of HP-β-CyD. Also, FA-HP-CyD induced the formation of autophagosomes in AML cell lines. FA-HP-β-CyD increased the inhibitory effects of cytarabine and a BCL-2-selective inhibitor, Venetoclax, which are commonly used treat elderly AML patients. Notably, FA-HP-β-CyD suppressed the proliferation of AML cells in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double-deficient mice with AML. These results suggest that FA-HP-β-CyD acts as a potent anticancer agent for AML chemotherapy by regulating.

IJMS | Free Full-Text | Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells (

Figure 2
FA-HP-β-CyD induces apoptosis in HL-60, THP1, SKM1, and Kasumi1 cells. (A) HL-60, THP1, SKM1, and Kasumi1 cells were treated with 0 (medium only), 0.5, 1.0, and 1.5 mM of FA-HP-β-CyD for 72 h. After 72 h, cells were stained with Annexin V and PI. Representative FCM plots are shown (n = 3). (BE) Percentage of Annexin V-positive PI-negative cells after exposure to FA-HP-β-CyD for 72 h. (B) HL-60, (C) THP1, (D) Kasumi1, (E) SKM1 cells. Data represent the mean ± SEM of three independent experiments. * p < 0.05.

Cyclodextrin supramolecular drug for targeted delivery of camptothecin as well as preparation method and application of cyclodextrin supramolecular drug

We believe that using cyclodextrin for targeted delivery of molecules is certainly one of the applications that will be in future’s research focus.

In this patent that we bring today as a good example, a camptothecin derivative and cyclodextrin polyrotaxane are subjected to a click chemical reaction under the catalysis of copper, and the cyclodextrin supramolecular drug for targeted delivery of camptothecin is obtained by using active folate termination. Cell experiments show that the compound has good targeting selectivity and anti-tumor effect, and also has the advantage of small toxic and side effects.

Espacenet – Cyclodextrin supramolecular drug for targeted delivery of camptothecin as well as preparation method and application of cyclodextrin supramolecular drug

Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells

What a great day! One of our youngest, Kristóf Felegyi just placed another brick in the wall of his PhD with this article about isolating and identifying novel polyporenic acids and triterpenes from Buglossoporus quercinus. The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.
Nice work and way to go, Kristof!

JoF | Free Full-Text | Polyporenic Acids from the Mushroom Buglossoporus quercinus Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells (

Novel targets for immune-checkpoint inhibition in cancer

Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer, highlight their biology, emphasizes the current understanding of resistance mechanisms, and focuses on promising strategies that are under investigation. Current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients are also collected.

Novel targets for immune-checkpoint inhibition in cancer – Cancer Treatment Reviews

2-Hydroxypropyl-β-cyclodextrin (HPβCD) as a Potential Therapeutic Agent for Breast Cancer

today’s cyclodextrin:
Breast cancer is a global burden with the most severe subtype being triple-negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule. Treatment with the cholesterol-depletory agent 2-hydroxypropyl-β-cyclodextrin (HPβCD) impeded the growth of cancer cells and further led to cancer cell death, which could be attributed to an altered cellular cholesterol profile following treatment. Furthermore, mice xenograft studies indicated complete eradication of early-stage tumours with no relapse, followed by a remarkable reduction in intermediate- and late-stage tumours, respectively. SFRP1 was identified as a possible molecular target facilitating the therapeutic action of HPβCD. These findings consequently potentiate cholesterol depletion as a novel anticancer strategy to be pursued.

University of the Witwatersrand – Tawanda ZiningaReubina WadeeMandeep Kaur et al

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Mechanisms of cancer resistance in long-lived mammals

Have you known that certain animals are unable to develop cancer? Do you also know why?

Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly, and are highly prone to cancer. They have been very useful for modeling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique traits of very high value to humans, such as cancer resistance and longevity. In recent years, several discoveries have been made in non-standard mammalian species, providing new insights into the natural mechanisms of cancer resistance. These include mechanisms of cancer resistance in the naked mole rat, blind mole rat, and elephant. In each of these species, evolution took a different path, leading to novel mechanisms. Many other long-lived mammalian species display cancer resistance, including whales, grey squirrels, microbats, cows, and horses. Understanding the molecular mechanisms of cancer resistance in all these species is important and timely, as, ultimately, these mechanisms could be harnessed for the development of human cancer therapies.

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Reduction of thyroid radioactive iodine exposure by oral administration of cyclic oligosaccharides

Radioactive iodine may cause thyroid cancer and hypofunction and accordingly must be properly managed. If the absorption of radioactive iodine is suppressed, it can be expected to lead to a reduction in thyroid exposure. This study the inhibition of radioactive iodine absorption by the oral administration of α-cyclodextrin is shown in a murine model. The uptake of radioactive iodine into the thyroid gland in mice administered with radioactive iodine and an α-cyclodextrin solution was approximately 40% lower after 24 h. The finding that oral uptake of α-cyclodextrin has an inhibitory effect on the transfer of radioactive iodine to the thyroid gland has potential for application in many fields such as food, pharmaceuticals, nuclear emergency preparedness, and medicine.
Kumamoto University, JAPAN

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A saliva-specific fucosylated structure-based sugar profile

A saliva-specific fucosylated structure-based sugar profile seems to be an efficent cancer diagnostic tool as claimed by Soochow University.
From the human saliva sample proteins extracted, subjected to enzymolysis and enriched in glycans from glycoproteins. Structural analysis and quantitative analysis of abundance on the glycans by means of mass spectrometry determines a glycan profile in the sample. By analyzing healthy saliva, non-cancer saliva, and lung cancer saliva, sugar profiles of high-abundance core fucose and branched fucose are identified. The method can be applied to clinical screening of lung cancer. The saliva-specific fucosylated structure-based sugar profile and the detection method therefor facilitate early diagnosis, feature easy-to-collect samples, and are not harmful to a patient, and thus have an excellent application prospect and important significance in the aspects of early screening and treatment of high-morbidity and high-death-rate lung cancer.

See the full patent here

Insights into recent preclinical studies on labeled cyclodextrin-based imaging probes: Towards a novel oncological era

today’s cyclodextrin:
is a beautiful review on labeled CD-based imaging probes from University of Debrecen (Zita Képes, István Hajdu, Ferenc Fenyvesi, and György Trencsényi).
As malignancies remain one of the major health concerns worldwide, increasing focus has been centered on the application of cyclodextrins (CDs) in cancer imaging and therapy due to their outstanding inclusion-forming capability. Studies applying fluorescently- CDs, or CD-based MRI contrast agents revealed much about pharmacokinetics and diagnostic applications; however, derivatives labeled with positron emitters seem superior molecular probes in the investigation of the route of CDs in the biological niche. Exploiting the firm signaling interaction between cancer-related cyclooxygenase-2, prostaglandin E2 (PGE2), and RAS oncoprotein, radioconjugated, PGE2-affine CDs project the establishment of novel imaging probes and therapeutic agents. 

See the full article here: Insights into recent preclinical studies on labelled cyclodextrin-based imaging probes: Towards a novel oncological era