Curcumin Recognizes a Unique Binding Site of Tubulin

Chakraborti, Soumyananda; Das, Lalita; Kapoor, Neha; Das, Amlan; Dwivedi, Vishnu; Poddar, Asim; Chakraborti, Gopal; Janik, Mark E.; Basu, Gautam; Panda, Dulal; Chakrabarti, Pinak; Surolia, Avadhesha; Bhattacharyya, Bhabatarak

doi:10.1021/jm2004046

Cited by 95 publications

(123 citation statements)

References 41 publications

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“…On the other hand, neurite outgrowth depends on the coordinated work of actin and microtubules to establish cytoskeletal networks and neurite morphology. Previous reports showed that curcumin affects the microtubule dynamics and SMN plays a role in the actin dynamics by affecting actin-binding/regulating proteins [30, 52]. Low levels of SMN protein may disrupt the cytoskeletal protein interactions and regulating pathways, which could be a possible explanation of why, in our study, the SMN knockdown cells were unresponsive to curcumin but the wild-type PC12 cells were not.…”

Section: Discussionmentioning

confidence: 46%

Investigations of Curcumin and Resveratrol on Neurite Outgrowth: Perspectives on Spinal Muscular Atrophy

Bora-Tatar

Erdem‐Yurter

2014

BioMed Research International

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Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease with progressive muscle weakness and atrophy. SMA is caused by low levels of the Survival of Motor Neuron (SMN) protein, which also leads to neurite outgrowth defects in neuronal cells. Rescue of the outgrowth defect is thought to be a strategy for SMA treatment. Polyphenolic histone deacetylase (HDAC) inhibitors might be good candidates due to their neuritogenic properties. In the present study, it was investigated whether neurite outgrowth defects could be rescued by curcumin and resveratrol, which are SMN-inducing polyphenols, having HDAC inhibition activity. According to our results, although curcumin and resveratrol failed to restore the neurite outgrowth defects, the SMN protein was found to be necessary for the neurite-promoting activity of curcumin in neuron-like PC12 cells.

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Section: Discussionmentioning

confidence: 46%

Investigations of Curcumin and Resveratrol on Neurite Outgrowth: Perspectives on Spinal Muscular Atrophy

Bora-Tatar

Erdem‐Yurter

2014

BioMed Research International

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“…Using fluorescence spectroscopy, Chakraborti et al demonstrated that curcumin, which is known for its anticarcinogenic properties, binds tubulin at a distance 32Å away from the colchicine-binding site. Docking studies suggested that the curcumin-binding site is localized close to the vinblastine-binding site [20]. The vinca alkaloids were the first natural products to enter clinical use.…”

Section: Introductionmentioning

confidence: 99%

Tubulin-interactive stilbene derivatives as anticancer agents

Mikstacka

Stefański

Różański

2013

Cellular and Molecular Biology Letters

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Microtubules are dynamic polymers that occur in eukaryotic cells and play important roles in cell division, motility, transport and signaling. They form during the process of polymerization of α- and β-tubulin dimers. Tubulin is a significant and heavily researched molecular target for anticancer drugs. Combretastatins are natural cis-stilbenes that exhibit cytotoxic properties in cultured cancer cells in vitro. Combretastatin A-4 (3′-hydroxy-3,4,4′, 5-tetramethoxy-cis-stilbene; CA-4) is a potent cytotoxic cis-stilbene that binds to β-tubulin at the colchicine-binding site and inhibits tubulin polymerization. The prodrug CA-4 phosphate is currently in clinical trials as a chemotherapeutic agent for cancer treatment. Numerous series of stilbene analogs have been studied in search of potent cytotoxic agents with the requisite tubulin-interactive properties. Microtubule-interfering agents include numerous CA-4 and transresveratrol analogs and other synthetic stilbene derivatives. Importantly, these agents are active in both tumor cells and immature endothelial cells of tumor blood vessels, where they inhibit the process of angiogenesis. Recently, computer-aided virtual screening was used to select potent tubulin-interactive compounds. This review covers the role of stilbene derivatives as a class of antitumor agents that act by targeting microtubule assembly dynamics. Additionally, we present the results of molecular modeling of their binding to specific sites on the α- and β-tubulin heterodimer. This has enabled the elucidation of the mechanism of stilbene cytotoxicity and is useful in the design of novel agents with improved anti-mitotic activity. Tubulin-interactive agents are believed to have the potential to play a significant role in the fight against cancer.

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“…Also, curcumin has recently been shown to bind with tubulin protein, at a location 32 Å away from the classical colchicine-binding site (Chakraborti et al, 2011). These previous reports, however, lack evidence of curcumin specificity for disrupting mitosis exclusively in cancerous cells.…”

Section: Discussionmentioning

confidence: 99%

Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation

Jackson

Murphy

Venema

et al. 2013

Food and Chemical Toxicology

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Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, we provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin’s ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2 µM threshold required to induce hemeoxy-genase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1 µM curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing.

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Curcumin Recognizes a Unique Binding Site of Tubulin

Cited by 95 publications

References 41 publications

Investigations of Curcumin and Resveratrol on Neurite Outgrowth: Perspectives on Spinal Muscular Atrophy

Investigations of Curcumin and Resveratrol on Neurite Outgrowth: Perspectives on Spinal Muscular Atrophy

Tubulin-interactive stilbene derivatives as anticancer agents

Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation

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