Curcumin mediated apoptosis in AK‐5 tumor cells involves the production of reactive oxygen intermediates

Bhaumik, Sraboni; Anjum, Rana; Rangaraj, Nandini; Pardhasaradhi, B.V.V.; Khar, Ashok

doi:10.1016/s0014-5793(99)00969-2

Cited by 185 publications

(131 citation statements)

References 31 publications

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“…Our results are in agreement with previous findings suggesting that ROS are needed for the apoptotic effects of curcumin [18,[58][59][60][61][62]. Indeed, we found that depletion of endogenous GSH augmented curcumin-induced cell death in tumor cells.…”

Section: Discussionsupporting

confidence: 94%

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Sandur

Ichikawa

Pandey

et al. 2007

Free Radical Biology and Medicine

275

172

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Extensive research within last half a century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits antioxidant, anti-inflammatory and proapoptotic activities. Whether anti-inflammatory and proapoptotic activities assigned to curcumin, are mediated through its antioxidant mechanism was investigated. We found that TNF-mediated NF-κB activation was inhibited by curcumin; and glutathione reversed the inhibition. Similarly, suppression of TNFinduced AKT activation by curcumin, was also abrogated by glutathione. The reducing agent also counteracted the inhibitory effect of curcumin on TNF-induced NF-κB regulated antiapoptotic (Bcl-2, Bcl-xL, IAP1), proliferative (cyclin D1) and proinflammatory (COX-2, iNOS and MMP-9) gene products. The suppression of TNF-induced AP-1 activation by curcumin was also reversed by glutathione. Also, the direct proapoptotic effects of curcumin were inhibited by glutathione and potentiated by depletion of intracellular glutathione by buthionine sulfoximine. Moreover, curcumin induced the production of reactive oxygen species (ROS) and modulated the intracellular GSH levels. Quenchers of hydroxyl radicals, however, were ineffective in inhibiting curcumin mediated NF-κB suppression. Further, N-acetylcysteine partially reversed the effect of curcumin. Based on these results we conclude that curcumin mediate its apoptotic and anti-inflammatory activities through modulation of the redox status of the cell.

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Section: Discussionsupporting

confidence: 94%

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Sandur

Ichikawa

Pandey

et al. 2007

Free Radical Biology and Medicine

275

172

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“…These results are in agreement with previous reports that showed that curcumin suppresses the proliferation of a wide variety of tumor cells (Mehta et al, 1997;Anto et al, 2002;Kuo et al, 1996;Jiang et al, 1996;Ranjan et al, 1999;Piwocka et al, 1999;Han et al, 1999;Simon et al, 1998;Ramachandran and You, 1999;Bhaumik et al, 1999), including both B cell and T cell leukemia, colon carcinoma, breast carcinoma, prostate cancer cells and other tumor cell types. How curcumin suppresses the proliferation of tumor cells is not well understood.…”

Section: Figuresupporting

confidence: 93%

“…We and others have previously shown that curcumin (diferuloylmethane), a chemopreventive agent, is a potent down-regulator of NF-kB activation, most likely through the suppression of IkBa kinase (IKK) needed for NF-kB activation and it inhibits NFkB-mediated gene expression (Singh and Aggarwal, 1995;Kumar et al, 1998;Plummer et al, 1999;Jobin et al, 1999). Curcumin is also known to suppress the proliferation of a wide variety of tumor cells, including breast and prostate cancer cells (Mehta et al, 1997;Anto et al, 2002;Kuo et al, 1996;Jiang et al, 1996;Ranjan et al, 1999;Piwocka et al, 1999;Han et al, 1999;Simon et al, 1998;Ramachandran and You, 1999;Bhaumik et al, 1999), through a mechanism which is incompletely understood. We hypothesized that curcumin must mediate its antiproliferative effects through down-regulation of cyclin D1.…”

Section: Introductionmentioning

confidence: 99%

Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation

et al. 2002

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Cyclin D1 is a proto-oncogene that is overexpressed in many cancers including breast and prostate. It plays a role in cell proliferation through activation of cyclin-dependent kinases. Curcumin, a diferuloylmethane, is a chemopreventive agent known to inhibit the proliferation of several breast and prostate cancer cell lines. It is possible that the effect of curcumin is mediated through the regulation of cyclin D1. In the present report we show that inhibition of the proliferation of various prostate, breast and squamous cell carcinoma cell lines by curcumin correlated with the down-regulation of the expression of cyclin D1 protein. In comparison, the down-regulation by curcumin of cyclin D2 and cyclin D3 was found only in selective cell lines. The suppression of cyclin D1 by curcumin led to inhibition of CDK4-mediated phosphorylation of retinoblastoma protein. We found that curcumin-induced down-regulation of cyclin D1 was inhibited by lactacystin, an inhibitor of 26S proteosome, suggesting that curcumin represses cyclin D1 expression by promoting proteolysis. We found that curcumin also down-regulated mRNA expression, thus suggesting transcriptional regulation. Curcumin also inhibited the activity of the cyclin D1 promoter-dependent reporter gene expression. Overall our results suggest that curcumin down-regulates cyclin D1 expression through activation of both transcriptional and post-transcriptional mechanisms, and this may contribute to the antiproliferative effects of curcumin against various cell types.

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“…2013), and prostate cancer cells (Chen, 2015). A high correlation was found between curcumin-mediated apoptosis and intracellular ROS (Bhaumik et al, 1999). A recent study reported that curcumin inhibits proliferation of colon cancer cell lines by arresting cells in G2-M phase (Hanif et al, 1997), down-regulates the expression of bcl-2 in tumor cells and induces apoptosis in NIH3T3 and leukemic cell line HL-60 (Jiang et al, 1996;Kuo et al, 1996).…”

Section: Introductionmentioning

confidence: 92%

A comparative study on the antioxidant and immunomodulatory properties of curcumin conjugated gold nanospheres and free curcumin

2017

J App Pharm Sci

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Curcumin, a phenolic compound isolated from the rhizomes of the plant Curcuma longa, has been known for decades. Owing to the fact of its hydrophobic nature and rapid metabolization, it has not been used as an effective drug so far. To solve the problem of bioavailability of curcumin, gold nanoparticles (cAuNps) reduced and stabilized with curcumin have been prepared. Afterwards, study for their antioxidant defenses and its effect on oxidative stress has been implemented. Cell cytotoxicity of both cAuNps (2.91677×10 2 -2.91677×10 12 particles ml -1 ) and free curcumin (1mM-128mM) were studied by 3-(4, 5-dimethylazol-2-yl)-2, 5-diphenyltetrazolium bromide) (MTT) assay. From the above studies, it was found that cAuNps could ameliorate the antioxidants defenses and could quench the ROS and RNS generated in the cells more significantly compared to free curcumin. This phenomenon is due to the abstraction of H atoms from phenolic functional groups of curcumin in the nanoconjugate form. Thus, the study proposes a strategy for increasing the bioavailability of curcumin as a therapeutic agent as well as increasing its activity due to the synergistic effect of gold conjugated to it.

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Curcumin mediated apoptosis in AK‐5 tumor cells involves the production of reactive oxygen intermediates

Cited by 185 publications

References 31 publications

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation

A comparative study on the antioxidant and immunomodulatory properties of curcumin conjugated gold nanospheres and free curcumin

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