Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA

Yodkeeree, Supachai; Chaiwangyen, Wittaya; Garbisa, Spiridione; Limtrakul, Pornngarm

doi:10.1016/j.jnutbio.2007.12.003

Cited by 165 publications

(109 citation statements)

References 36 publications

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“…We also investigated whether DMC could inhibit PC-3 cells migration and invasion. Results from woundhealing assays demonstrated that in DMC treated groups (20,40 and 80 µM) the migrating cells in the scratched area were significantly reduced to 62.3, 49.2 and 22.6%, respectively, compared with the control group (Fig. 4A).…”

Section: A B C Dmentioning

confidence: 93%

Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells

Zhang

Zhao

et al. 2012

Oncol Rep

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Abstract. Curcumin (CUR) is a natural agent that has been demonstrated to effectively inhibit prostate cancer growth. However, natural CUR is relatively unstable and can be easily degraded in vivo. Therefore, it is essential to develop other stable curcuminoids. Demethoxycurcumin (DMC) is a candidate that has been verified in several tumor types and has potential for the treatment of prostate cancer. In the present study, we investigated the effects of DMC on proliferation, apoptosis and migration of PC-3 cells. MTT assay results indicated that DMC inhibited PC-3 cell viability in a dose-and time-dependent manner, and DMC induced G2/M phase arrest. Furthermore, PC-3 cells in DMC-treated groups had a higher apoptotic rate compared with DMSO-treated control. This effect may be due to the activation of the caspase-3 pathway. In DMC-treated groups, migrating and invasive cells were dramatically reduced (P<0.05). The activity of MMP-2, which is correlated with migration and invasion was also suppressed by DMC. These results indicated that DMC may inhibit PC-3 cell migration and invasion partially by affecting MMP-2 activity. In conclusion, DMC significantly inhibits proliferation, migration and invasion of cultured PC-3 cells, and this study may provide evidence for future in vivo studies and clinical use. IntroductionProstate cancer is a common urologic malignant tumor, which is threatening more and more people currently. The emerging studies on cancer prevention and treatment with natural products expand the traditional treatment of prostate cancer (1). Curcuminoids are phenolic coloring compounds that can be extracted from the rhizomes of Curcuma longa linn. Curcumin (CUR), a member of curcuminoids, has potent anti-tumor effects to prostate cancer (2-4) and several other cancers, such as breast (5) and colon cancer (6). However, CUR can be easily degraded both in vitro and in vivo (7,8). The anti-tumor activity of CUR will be enormously reduced, and this instability property of CUR limits its clinical use in cancer treatment. It is feasible to develop new stable compounds that are structurally similar as CUR but without the loss of anti-tumor activity. Demethoxycurcumin (DMC), an analogue of CUR, is one of such compounds. In comparison with CUR, the structure of DMC lacks one methoxy group directly linking to the benzene ring (Fig. 1). Although the structure difference between CUR and DMC is slight, the chemical characteristics of DMC is more stable (9,10). Previous studies have reported that DMC could inhibit renal and breast cancer cell growth (11,12) and induce G2/M phase arrest and apoptosis in human glioma U87 cells (13). These studies provide evidence that DMC might be a good substitute for CUR in cancer treatment. However, the effects of DMC on prostate cancer cells still remain unclear. Therefore, the present study was designed to investigate the effects of DMC on proliferation, apoptosis, migration and invasion in cultured human prostate cancer cells. In order to further explore the mechanisms of DMC on c...

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Section: A B C Dmentioning

confidence: 93%

Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells

Zhang

Zhao

et al. 2012

Oncol Rep

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“…Extensive research during the last half century has revealed several important functions of curcumin such as antioxidant, anti-inflammatory and anticancer properties (5)(6)(7). Recently, more and more studies have demonstrated the stronger activity of DMC when compared with curcumin in many aspects (8)(9)(10). Numerous studies have shown that DMC induces cytotoxic effects in many cancer cell lines such as colon (11) and renal cell cancer (12), glioma (9) and leukemic cell lines (13).…”

Section: Introductionmentioning

confidence: 99%

Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

Lien

Liu

et al. 2015

Oncology Reports

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Abstract. Lung cancer is the most common cause of cancerrelated mortality in the US as well as other regions of the world. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major components of Curcuma longa L. It has been reported that curcumin inhibits the growth of various types of cancer cells in vitro and in vivo. However, the mechanisms involved in the inhibition of cell growth and induced apoptosis by DMC in human lung cancer cells remain unclear. In the present study, we investigated the effect of DMC on cell death via the induction of apoptosis in NCI-H460 human lung cancer cells. Flow cytometric assay was used to examine the total percentage of viable cells, the population of cells in the sub-G1 phase of the cell cycle, the level of reactive oxygen species (ROS), Ca 2+ production, mitochondrial membrane potential (ΔΨm) and caspase activity. Western blotting was used to examine the changes in the expression of cell cycle-and apoptosis-associated proteins. Confocal microscopy was used to examine the translocation of apoptosis-associated proteins. The results indicated that DMC significantly induced cell morphological changes and decreased the percentage of viable NCI-H460 cells and DMC induced apoptosis based on the cell distribution in the sub-G1 phase. Moreover, DMC promoted ROS and Ca 2+ production and decreased the level of ΔΨm and promoted the activities of caspase-3, -8 and -9. The Western blotting results showed that DMC promoted the expression of AIF, Endo G and PARP. The levels of Fas ligand (Fas L) and Fas were also upregulated. Furthermore, DMC promoted expression of ER stress-associated proteins such as GRP78, GADD153, IRE1β, ATF-6α, ATF-6β and caspase-4. Based on the findings, we suggest that DMC may be used as a novel anticancer agent for the treatment of lung cancer in the future.

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“…bDMC shows higher cytotoxicity against human ovarian cancer cell line, increased antimutagenic, anticarcinogenic and antioxidant activity (reviewed in [25]). The inhibition of cancer cell invasion by bDMC highlights its enhanced A c c e p t e d M a n u s c r i p t 4 antimetastasis potency [26]. The synthetic derivative DAC shows higher antibacterial activity against multiresistant bacteria [27] and a stronger nitric oxide (NO) and O 2 •-anion scavenging activity [28,29], although it has slightly lower apoptotic activity on AK-5 rat histiocytoma cells [30].…”

Section: Introductionmentioning

confidence: 99%

Curcumin derivatives: Molecular basis of their anti-cancer activity

Basile

Ferrari

Lazzari

et al. 2009

Biochemical Pharmacology

160

125

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Curcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of chemopreventive, anti-oxidant and anti-tumor properties. Although its promising chemotherapeutic activity, preclinical and clinical studies highlight Curcumin limited therapeutic application due to its instability in physiological conditions. To improve its stability and activity, many derivatives have been synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more stable than Curcumin in physiological medium. To explore the mechanism of their chemotherapeutic effect, we studied their role in proliferation in the HCT116 human colon cancer cells. We correlated kinetic stability and cellular uptake data to their biological effects. Both bDMC and DAC impair correct spindles formation and induce a p53-and p21 CIP1/WAF1 -independent mitotic arrest, which is more stable and long-lasting for bDMC. A subsequent p53/p21 CIP1/WAF1 -dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a consequence of the mitotic slippage, preventing postmitotic cells from re-entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct effect of the drug and concomitant to the mitotic block. Finally, we demonstrate that bDMC induces rapid DNA double-strand breaks, moving for its possible development in anti-cancer clinical applications.

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Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA

Cited by 165 publications

References 36 publications

Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells

Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells

Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

Curcumin derivatives: Molecular basis of their anti-cancer activity

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