Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL

Rashmi, Ramachandran; Kumar, Sunil; Karunagaran, Devarajan

doi:10.1093/carcin/bgi025

Cited by 77 publications

(57 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are studies that have shown that cells lacking Bax in colon cancer cells and mouse embryonic fibroblasts lacking Bax/Bak showed resistance to curcumin-induced apoptosis (46,47). In both these studies, resistance to curcumin treatment was overcome by overexpression of second mitochondrial derived activator of caspase.…”

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

View full text Add to dashboard Cite

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]

show abstract

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

View full text Add to dashboard Cite

show abstract

“…The current study suggests that SMAC plays an important role in executing DNA damage-induced and PUMA-mediated apoptosis by participating in a feedback amplification loop and other mitochondrial events, which implies that SMAC enhances the antitumor activities of chemotherapeutic drugs and irradiation by promoting the proapoptotic function of PUMA. Although SMAC release is a general response to different apoptotic stimuli (Deng et al, 2002;Arnt and Kaufmann, 2003;Rashmi et al, 2005), the requirement of SMAC in apoptosis appears to be somewhat specific. Among a number of stimuli analysed, only a few, including Ad-PUMA, NSAIDs and certain DNA-damaging agents, were found to induce SMAC-dependent apoptosis and caspase activation (Kohli et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

SMAC/Diablo mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events

Wang

Ming

et al. 2007

Oncogene

View full text Add to dashboard Cite

“…Bax is known to form large lipidic pores through which high molecular weight molecules can pass (Bleicken et al, 2010). Rashmi et al (2005) have shown role of Bax in curcumin-induced apoptosis using isogenic human colon cancer cells (HCT 116). The results from their study suggest that Bax deficiency almost completely prevented the release of Cytochrome C, AIF and Smac with subsequent inhibition of caspases 3, 8 and 9.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Conjugates Induce Apoptosis Via a Mitochondrion Dependent Pathway in MCF-7 and MDA-MB-231 Cell Lines

Singh¹,

Agarwal²,

Singh³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. IC 50 values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (∆ψm) followed by inhibition of translocation of transcription factor NF-kB and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/ Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

show abstract

Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL

Cited by 77 publications

References 43 publications

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

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

SMAC/Diablo mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events

Curcumin Conjugates Induce Apoptosis Via a Mitochondrion Dependent Pathway in MCF-7 and MDA-MB-231 Cell Lines

Contact Info

Product

Resources

About