Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time- and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.

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Vitamin D as potential therapeutic anticancer agent

Journal of Cancer Science and Therapeutics ◽

10.36879/jcst.19.000106 ◽

2018 ◽

pp. 1-3

Keyword(s):

Vitamin D ◽

Anticancer Activity ◽

Anticancer Agent ◽

Antitumor Agents ◽

Metastatic Potential ◽

Anticancer Properties ◽

Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

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Thymic Immunosuppressive Pentapeptide (TIPP) Showed Anticancer Activity in Breast Cancer and Chronic Myeloid Leukemia Both In Vitro and In Vivo

Protein and Peptide Letters ◽

10.2174/0929866528666210622150500 ◽

2021 ◽

Vol 28 ◽

Author(s):

Muhammad Ijaz ◽

Muhammad Shahbaz ◽

Wenjie Jiang ◽

Yikang Shi ◽

Xiuli Guo ◽

...

Keyword(s):

Breast Cancer ◽

Chronic Myeloid Leukemia ◽

Anticancer Activity ◽

Myeloid Leukemia ◽

Map Kinases ◽

Inflammatory Responses ◽

Tumor Xenograft ◽

Immunohistochemistry Analysis

Aim: Being the common cause and major burden of deaths globally, timely management of cancer is crucial. Background: Thymic immunosuppressive pentapeptide (TIPP) is a novel pentapeptide originally obtained from calf thymic immunosuppressive extract. Previously, TIPP has been proved to suppress the allergic and inflammatory responses in allergic mice via blocking MAP kinases/NF-κB signaling pathways. Objective: In this study, in vitro anticancer activity of TIPP was tested on two different types of cancers using MCF-7 and K562 cell lines. Methods: Tumor xenograft models for breast cancer and chronic myeloid leukemia were designed. In vivo anticancer activity of TIPP was investigated on both cancer types. The liver and tumor tissues of the mice were preserved for immunohistochemistry analysis. Results: In vitro anticancer activity of TIPP showed significant inhibition on cell viability of both breast cancer and chronic myeloid leukemia. In vivo anticancer effect of TIPP in both types of cancer models further proved the potent anticancer nature of TIPP. Immunohistochemistry analysis assured that TIPP is a safe drug for normal organs such as the liver. Conclusion: Our present study revealed that TIPP is a potent anticancer drug and an important treatment option for various diseases. Further work is needed to test the flexible and proficient activity of the novel peptide.

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Przeciwnowotworowe działanie składników propolisu. Cz. 1. Ester fenyloetylowy kwasu kawowego (CAPE)

Postępy Fitoterapii ◽

10.25121/pf.2020.21.3.177 ◽

2020 ◽

Vol 21 (3) ◽

Author(s):

Bogdan Kędzia ◽

Elżbieta Hołderna-Kędzia

Keyword(s):

Human Colon ◽

Caffeic Acid Phenethyl Ester ◽

Biological Properties ◽

Biologically Active ◽

Significant Activity ◽

Colon Adenoma ◽

Cancer Cell Survival ◽

Ht 29

The paper presents a review of the publications on the anticancerogenic activity of the biologically active component of propolis – caffeic acid phenethyl ester (CAPE). Literature data indicate numerous biological properties of CAPE, namely: antioxidant, anti-inflammatory, antiviral, immunostimulatory, anti-angiogenic and others. In numerous tests, both in vitro and in vivo, the significant activity of CAPE has been confirmed, including an action against HT-29 human colon adenoma cells, and five: human, murine and other tumor cell cultures. The authors also emphasize that CAPE supports the anticancerogenic effect of drugs, including doxorubicin and cisplatin, due to the reduction of cancer cell survival by 45% and 34%, respectively, compared to the above-mentioned drugs used alone. The conducted research indicates that the induction of apoptosis in cells, i.e. programmed cell death, can be mentioned among the main mechanisms of the anticancerogenic activity of CAPE.

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Sensitizing human colon carcinoma HT-29 cells to cisplatin by cyclopentenylcytosine, in vitro and in vivo

Life Sciences ◽

10.1016/s0024-3205(00)00914-0 ◽

2000 ◽

Vol 68 (1) ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Kamran Gharehbaghi ◽

Thomas Szekeres ◽

Joel A. Yalowitz ◽

Monika Fritzer-Szekeres ◽

Yves G. Pommier ◽

...

Keyword(s):

Colon Carcinoma ◽

Human Colon ◽

Human Colon Carcinoma ◽

Ht 29

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Synthesis, CYP24A1-Dependent Metabolism and Antiproliferative Potential against Colorectal Cancer Cells of 1,25-Dihydroxyvitamin D2 Derivatives Modified at the Side Chain and the A-Ring

International Journal of Molecular Sciences ◽

10.3390/ijms21020642 ◽

2020 ◽

Vol 21 (2) ◽

pp. 642

Author(s):

Magdalena Milczarek ◽

Michał Chodyński ◽

Anita Pietraszek ◽

Martyna Stachowicz-Suhs ◽

Kaori Yasuda ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Biologically Active ◽

Side Chain ◽

Anticancer Properties ◽

Colorectal Cancer Cells ◽

Ht 29

Experimental data indicate that low-calcemic vitamin D derivatives (VDDs) exhibit anticancer properties, both in vitro and in vivo. In our search for a vitamin D analog as potential anticancer agent, we investigated the influence of chirality in the side chain of the derivatives of 1,25-dihydroxyergocalciferol (1,25D2) on their activities. In this study, we synthesized modified analogs at the side chain and the A-ring, which differed from one another in their absolute configuration at C-24, namely (24S)- and (24R)-1,25-dihydroxy-19-nor-20a-homo-ergocalciferols (PRI-5105 and PRI-5106, respectively), and evaluated their activity. Unexpectedly, despite introducing double-point modifications, both analogs served as very good substrates for the vitamin D-hydroxylating enzyme. Irrespective of their absolute C-24 configuration, PRI-5105 and PRI-5106 showed relatively low resistance to CYP24A1-dependent metabolic deactivation. Additionally, both VDDs revealed a similar antiproliferative activity against HT-29 colorectal cancer cells which was higher than that of 1,25D3, the major biologically active metabolite of vitamin D. Furthermore, PRI-5105 and PRI-5106 significantly enhanced the cell growth-inhibitory activity of 5-fluorouracil on HT-29 cell line. In conclusion, although the two derivatives showed a relatively high anticancer potential, they exhibited undesired high metabolic conversion.

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mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

Pharmaceutics ◽

10.3390/pharmaceutics12070676 ◽

2020 ◽

Vol 12 (7) ◽

pp. 676

Author(s):

Marie Millard ◽

Solène Posty ◽

Max Piffoux ◽

Jordane Jasniewski ◽

Henri-Pierre Lassalle ◽

...

Keyword(s):

Extracellular Vesicles ◽

Human Colon ◽

Bilayer Membrane ◽

Phospholipid Bilayer ◽

Phospholipid Bilayer Membrane ◽

Photodynamic Activity ◽

Ht 29 ◽

Determinant Factor

Extracellular vesicles (EVs), derived from the cell, display a phospholipid bilayer membrane that protects the cargo molecules from degradation and contributes to increasing their stability in the bloodstream and tumor targeting. EVs are interesting in regard to the delivery of photosensitizers (PSs) used in the photodynamic therapy (PDT), as they allow us to overcome the limitations observed with liposomes. In fact, liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foslip®), one of the most potent clinically approved PSs, is rapidly destroyed in circulation, thus decreasing in vivo PDT efficacy. mTHPC-EV uptake was evaluated in vitro in a 3D human colon HT-29 microtumor and in vivo study was performed in HT-29 xenografted mice. The obtained data were compared with Foslip®. After intravenous injection of the mTHPC formulations, biodistribution, pharmacokinetics and PDT-induced tumor regrowth were evaluated. In a 3D model of cells, mTHPC-EV uptake featured a deeper penetration after 24h incubation compared to liposomal mTHPC. In vivo results showed a considerable improvement of 33% tumor cure with PDT treatment applied 24h after injection, while 0% was observed after Foslip®/PDT. Moreover, 47 days were required to obtain ten times the initial tumor volume after mTHPC-EVs/PDT compared to 30 days for liposomal mTHPC. In conclusion, compared to Foslip®, mTHPC-EVs improved mTHPC biodistribution and PDT efficacy in vivo. We deduced that a major determinant factor for the improved in vivo PDT efficacy is the deep mTHPC intratumor penetration.

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Potent in vivo anticancer activity and stability of liposomes encapsulated with semi-purified Job’s tear (Coix lacryma-jobi Linn.) extracts on human colon adenocarcinoma (HT-29) xenografted mice

Drug Delivery ◽

10.1080/10717544.2016.1189464 ◽

2016 ◽

Vol 23 (9) ◽

pp. 3399-3407 ◽

Cited By ~ 5

Author(s):

Mathukorn Sainakham ◽

Aranya Manosroi ◽

Masahiko Abe ◽

Worapaka Manosroi ◽

Jiradej Manosroi

Keyword(s):

Anticancer Activity ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Ht 29 ◽

Human Colon Adenocarcinoma

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The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

Cellular & Molecular Biology Letters ◽

10.2478/s11658-009-0001-9 ◽

2009 ◽

Vol 14 (2) ◽

Cited By ~ 27

Author(s):

Xiao Zhang ◽

Yin-Lin Ge ◽

Run-Hua Tian

Keyword(s):

Colon Cancer ◽

Polymerase Chain Reaction ◽

Reverse Transcription ◽

Human Colon ◽

Chain Reaction ◽

Human Colon Cancer ◽

Polymerase Chain ◽

Ht 29

AbstractWe investigated the effects of RNA interference-mediated silencing of the c-myc gene on celluar proliferation and apoptosis in human colon cancer HT-29 cells in vitro and in vivo. A small interfering RNA (siRNA) targeting c-myc was designed, the DNA template was synthesized, and the siRNA was obtained by in vitro transcription. After siRNA transfection into HT-29 and human neuroblastoma IMR-32 cells with Lipofectamine 2000™, the proliferation of the HT-29 and IMR-32 cells was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and Hoechst 33258 staining was used to observe cell apoptosis. Following gene transfer to HT-29 cells, the expression of c-myc mRNA was examined via reverse transcription polymerase chain reaction, and the level of the protein via Western blot assay. Growth curves were constructed and in vivo experiments were performed on nude mice to assess the effects of c-myc silencing on tumor growth. The c-myc expression in the tumor tissue was measured by reverse transcription polymerase chain reaction and subsequently by immunohistochemistry. Our paper demonstrates that the delivery of siRNA directed against c-myc not only efficiently down-regulated the expression of c-myc, inhibited the proliferation of HT-29 cells and induced apoptosis in vitro, but also suppressed the growth of colon cancer cells in vivo.

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Inclusion complexes of anhydrolycorine with cyclodextrins: preparation, characterization, and anticancer activity

Canadian Journal of Chemistry ◽

10.1139/cjc-2015-0462 ◽

2016 ◽

Vol 94 (6) ◽

pp. 575-582 ◽

Cited By ~ 6

Author(s):

Yafei Guo ◽

Jiuling Li ◽

Yuqi Liu ◽

Yongping Ma ◽

Huilin Cheng ◽

...

Keyword(s):

Colon Cancer ◽

Anticancer Activity ◽

Inclusion Complexes ◽

Water Solubility ◽

Inclusion Complexation ◽

Human Colon ◽

In Vitro Cytotoxicity ◽

Human Colon Cancer ◽

Ht 29

This article describes the preparation of a series of inclusion complexes of anhydrolycorine with three cyclodextrins (CDs), namely β-CD, γ-CD, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and their successful characterization through UV, TG, DSC, XRD, SEM, 1H NMR, and 2D NMR spectroscopies. The results demonstrated that the water solubility of anhydrolycorine increased notably by about 23–42 times after the inclusion complexation with these CDs. Furthermore, preliminary in vitro cytotoxicity experiments on human colon cancer cell lines HT-29, SW480, HCT116, and DLD-1 were also performed, and the complexes showed remarkable anticancer activity against HT-29, SW480, and HCT116. These results suggested that the inclusion complexes would be potentially useful for applications for human colon cancer chemotherapy.

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