Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

Chopra, Avijeet; Kuratnik, Anton; Scocchera, Eric W.; Wright, Dennis L.; Giardina, Charles

doi:10.4161/cbt.23787

Cited by 12 publications

(27 citation statements)

References 69 publications

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“…Analysis of the subdiploid cell population indicated that AK301, on its own, did not induce apoptosis in HT29 colon cancer cells. However, in the presence of TNF, AK301-treated cells underwent significant apoptosis (EC 50 of 172 nM) at concentrations ϳ5 times lower than those reported for AK3 (18).…”

Section: Tnf-dependent Induction Of Apoptosis In Ak301-treated Cells-ak3mentioning

confidence: 84%

“…Western Blot-RIPA buffer was used for total protein extraction and Nonidet P-40 buffer was used for membrane protein extraction (18). 20 g of protein was denatured under reducing conditions (27,28), separated on 4 -20% gradient gels (BioRad), and transferred to nitrocellulose by voltage gradient transfer.…”

Section: Methodsmentioning

confidence: 99%

“…and other piperazine-based compounds were originally identified by their ability to acutely sensitize colon cancer cells to ligand-induced apoptosis (18). To determine whether AK301 could also induce cell death in combination with TNF, we performed a dose-response analysis of AK301 in the presence and absence of TNF (Fig.…”

Section: Tnf-dependent Induction Of Apoptosis In Ak301-treated Cells-ak3mentioning

confidence: 99%

“…Cells-In previous studies, we identified the AK3 compound from the ChemBridge DIVERSet TM library that induced mitotic arrest in colon cancer cells at low micromolar concentrations (0.5-1 M) (18). To assess properties of the chlorophenyl and methoxybenzoyl functional groups of AK3, four different AK3 analogs were analyzed for their ability to induce mitotic arrest in HT29 colon cancer cells at 5 M (Fig.…”

Section: Functional Groups Of Ak3 Mediate Mitotic Arrest In Ht29mentioning

confidence: 99%

“…We previously reported several novel synthetic small molecules that dramatically increase colon cancer cell death by TNF and other death ligands, while being unable to induce apoptosis on their own (18). Interestingly, many of these compounds also induced mitotic arrest.…”

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confidence: 99%

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Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Chopra

Anderson

Giardina

2014

Journal of Biological Chemistry

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Background: Mitotic spindles are important targets of cancer chemotherapeutic agents. Results: A new class of tubulin-targeting agents is identified that effectively sensitizes colon cancer cells to ligand-induced apoptosis. Conclusion: AK301 is a novel, piperazine-based compound that induces mitotic arrest and increases ligand-dependent apoptosis. Significance: Mitotically active compounds that stimulate ligand-induced apoptotic signaling might be useful for augmenting immune-based cancer therapies.

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Section: Tnf-dependent Induction Of Apoptosis In Ak301-treated Cells-ak3mentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Tnf-dependent Induction Of Apoptosis In Ak301-treated Cells-ak3mentioning

confidence: 99%

Section: Functional Groups Of Ak3 Mediate Mitotic Arrest In Ht29mentioning

confidence: 99%

mentioning

confidence: 99%

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Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Chopra

Anderson

Giardina

2014

Journal of Biological Chemistry

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Evaluation of Polo‐like kinase 1 as a potential therapeutic target in Merkel cell carcinoma

et al. 2015

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Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy

Arnst

Banerjee

Chen

et al. 2019

Medicinal Research Reviews

122

107

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Microtubule (MT)‐targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Newer generations of developed drugs attack these problems and alternative approaches such as the development of dual tubulin and kinase inhibitors are being investigated. This approach offers the potential to show increased efficacy and lower toxicities. This review covers different categories of MT‐targeting agents, recent advances in dual inhibitors, and current challenges for this drug target.

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Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

Cited by 12 publications

References 69 publications

Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Evaluation of Polo‐like kinase 1 as a potential therapeutic target in Merkel cell carcinoma

Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy

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