Dose escalation of a curcuminoid formulation

Lao, Christopher D.; Ruffin, Mack T.; Normolle, Daniel P.; Heath, Dennis D.; Murray, Sandra I.; Bailey, Joanne; Boggs, Martha E.; Crowell, James A.; Rock, Cheryl L.; Brenner, Dean E.

doi:10.1186/1472-6882-6-10

Cited by 1,137 publications

(830 citation statements)

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“…An increasing number of studies have shown curcumin anticancer efficacy in preclinical and clinical settings (17). Several phase I clinical studies have also shown that curcumin was well tolerated up to 10 to 12 g (17,50). Furthermore, the combination of curcumin and TRAIL resulted in considerable apoptosis in tumors that do not express Bax such as Burkitt's lymphoma, which confers resistance to many conventional chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines

Hussain¹,

Ahmed²,

Al-Jomah³

et al. 2008

Molecular Cancer Therapeutics

112

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We provide evidence that curcumin, a natural compound isolated from rhizomes of plant Curcuma longa, induces apoptosis in several Burkitt's lymphoma cell lines expressing Bax protein (AS283A, KK124, and Pa682PB), whereas it has no effects in cell lines with no Bax expression (BML895 and CA46). Our data show that curcumin treatment results in down-regulation of constitutive activation of nuclear factor-KB (NF-KB) via generation of reactive oxygen species where it causes conformational changes in Bax protein leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and poly(ADP)-ribose polymerase cleavage leading to caspase-dependent apoptosis. In addition, curcumin treatment of Burkitt's lymphoma cell lines also causes upregulation of DR5; however, this up-regulation does not result in apoptosis. Importantly, cotreatment with curcumin and TRAIL induces apoptosis in Bax-deficient cell lines. Taken together, our findings suggest that curcumin is able to induce apoptosis in Bax-positive cell lines, whereas combinations with TRAIL result in apoptosis in Bax-negative cell lines. These findings also raise the possibility that incorporation of curcumin in treatment regimens may provide a novel approach for the treatment of Burkitt's lymphomas and provide the molecular basis for such future translational efforts. [Mol Cancer Ther 2008;7(10):3318 -29]

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Section: Discussionmentioning

confidence: 99%

Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines

Hussain¹,

Ahmed²,

Al-Jomah³

et al. 2008

Molecular Cancer Therapeutics

112

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“…In addition, oral intake of 8 g/d curcumin resulted in f2 Amol/L concentration in serum (56). A recent report detected low levels of curcumin after 8 g of oral dose, but it could be because of the type of formulation used, which had 66% less curcumin than the pure curcumin powder (57). Therefore, curcuminoid intake can be expected to result in concentrations high enough to increase the levels of the anticancer drugs in the cells through its inhibitory effect on ABCG2.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the function of the multidrug resistance–linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin

Chearwae

Shukla

Limtrakul

et al. 2006

Molecular Cancer Therapeutics

111

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Curcumin (curcumin I), demethoxycurcumin (curcumin II), and bisdemethoxycurcumin (curcumin III) are the major forms of curcuminoids found in the turmeric powder, which exhibit anticancer, antioxidant, and anti-inflammatory activities. In this study, we evaluated the ability of purified curcuminoids to modulate the function of either the wild-type 482R or the mutant 482T ABCG2 transporter stably expressed in HEK293 cells and drug-selected MCF-7 FLV1000 and MCF-7 AdVp3000 cells. Curcuminoids inhibited the transport of mitoxantrone and pheophorbide a from ABCG2-expressing cells. However, both cytotoxicity and [ 3 H]curcumin I accumulation assays showed that curcuminoids are not transported by ABCG2. Nontoxic concentration of curcumin I, II, and III sensitized the ABCG2-expressing cells to mitoxantrone, topotecan, SN-38, and doxorubicin. This reversal was not due to reduced expression because ABCG2 protein levels were unaltered by treatment with 10 Mmol/L curcuminoids for 72 hours. Curcumin I, II, and III stimulated (2.4-to 3.3-fold) ABCG2-mediated ATP hydrolysis and the IC 50 s were in the range of 7.5 to 18 nmol/L, suggesting a high affinity of curcuminoids for ABCG2. Curcuminoids also inhibited the photolabeling of ABCG2 with P]8-azidoATP to ABCG2, suggesting that they do not interact with the ATP-binding site of the transporter. Collectively, these data show that, among curcuminoids, curcumin I is the most potent modulator of ABCG2 and thus should be considered as a treatment to increase the efficacy of conventional chemotherapeutic drugs.

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“…Such effects include antioxidant [27], anti-inflammatory [24,28,29], anticarcinogenic and antimicrobial [30][31][32], hepatoprotective [32], thrombosuppressive [33], cardiovascular (i.e., as protection against myocardial infarction) [29,34,35], hypoglycemic [36][37][38], and antiarthritic (i.e., as protection against rheumatoid arthritis) [39], The most compelling and key rationale for the continuing traditional therapeutic use of curcumin is its extremely good safety profile. To date, no studies in either animals [40,41] or humans [42] have discovered any toxicity associated with the use of curcumin, and it is clear that curcumin is not toxic even at very high doses.…”

Section: Q4mentioning

confidence: 99%