Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and –independent apoptosis via Smad or Akt signaling pathways in HOS cells

Huang, Cheng; Lu, Hsu Feng; Chen, Yu-Hsuan; Chen, Jui Chieh; Chou, Wen Hsiang; Huang, Haoping

doi:10.1186/s12906-020-2857-1

Cited by 48 publications

(35 citation statements)

References 27 publications

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“…A previous study [41] has reported that curcuminoids suppress TNF-α-induced NF-κB activation in the order of BDMC < DMC < curcumin. The anti-breast cancer and anti-melanoma activities of BDMC were also less than curcumin and DMC in a cell-based study [42]. Although these investigations exhibited items to the contrary of our study, the superior chemical stability of BDMC over curcumin and DMC could be the reason for the observed stronger anti-adipogenic effect.…”

Section: Discussioncontrasting

confidence: 96%

The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

et al. 2021

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Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

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Section: Discussioncontrasting

confidence: 96%

The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

et al. 2021

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“…The chemical stability is better in bisdemethoxycurcumin than curcumin and demethoxycurcumin. 14 In contrast, demethoxycurcumin has one methoxy group, while curcumin has two methoxy groups. Therefore, the chemical stability is better in demethoxycurcumin than in curcumin.…”

Section: Discussionmentioning

confidence: 99%

“…28 Consistently, methoxy groups of curcumin analogues also played important anti-cancer effects in breast cancer, melanoma, and osteosarcoma. 14 Furthermore, Somparn et al 29 found that methoxy group associated with the antioxidant activity. In our results showed that curcumin, demethoxycurcumin and dimethoxycurcumin displayed the anti-cancer activities such as suppressed cell viability and colony formation in both LN229 and GBM8401 glioma cells.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Cancer Effect of Four Curcumin Analogues on Human Glioma Cells

Luo¹,

Wu²,

Huang³

et al. 2021

OTT

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Purpose Glioblastoma multiforme (GBM) is the primary aggressive malignancy of the brain with poor outcome. Curcumin analogues are polyphenolic compounds as the bioactive substances extracted from turmeric. This study aims to investigate the anti-cancer effects of four curcumin analogues. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot. Materials and Methods Human LN229 and GBM8401 glioma cells were treated by four curcumin analogues with different number of methoxy groups. The cell viability, cell cycle, apoptosis, proliferation and ROS production of human gliomas were analyzed by flow cytometry. Moreover, the effects of four curcumin analogues on tumorigenesis of gliomas were conducted by wound healing assay and colony formation assay. Furthermore, the molecular mechanisms of dimethoxycurcumin in human gliomas were analyzed by Western blot. Results Our data showed that four different curcumin analogues including curcumin, bisdemethoxycurcumin, demethoxycurcumin, and dimethoxycurcumin promote sub-G1 phase, G2/M arrest, apoptosis, and ROS production in human glioma cells. Moreover, dimethoxycurcumin suppressed cell viability, migration, and colony formation, induction of sub-G1, G2/M arrest, apoptosis, and ROS production in glioma cells. Moreover, the mechanism of dimethoxycurcumin is ROS production to increase LC3B-II expression to induce autophagy. Furthermore, dimethoxycurcumin suppressed apoptotic marker, BCL-2 to promote apoptosis in LN229 and GBM8401 glioma cells. Conclusion Our study found that dimethoxycurcumin induced apoptosis, autophagy, ROS production and suppressed cell viability in human gliomas. Dimethoxycurcumin might be a potential therapeutic candidate in human glioma cells.

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“…In year 2020, Huang et al suggested that curcumin and DMC showed better pro-apoptotic effect than BDMC in HOS osteosarcoma cells. 38 Furthermore, it was suggested that phenyl methoxy group may crucially affect direct inhibitory activity on NF-κB 39 . As a direct target of curcumin 40 , the interaction or binding with STAT3.may also be influenced by the presence of phenyl methoxy group, besides of the effect of diketone groups.…”

Section: Discussionmentioning

confidence: 99%

A Natural Degradant of Curcumin, Feruloylacetone Inhibits Cell Proliferation via Inducing Cell Cycle Arrest and a Mitochondrial Apoptotic Pathway in HCT116 Colon Cancer Cells

Chou¹,

Koh²,

Nagabhushanam

et al. 2021

Preprint

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Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart in previous studies and, therefore, its anti-cancer efficacy is investigated herein. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed the capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rised to 36.9% and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anti-cancer effect, and FER showed a greater pro-apoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.

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Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and –independent apoptosis via Smad or Akt signaling pathways in HOS cells

Cited by 48 publications

References 27 publications

The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

The Anti-Cancer Effect of Four Curcumin Analogues on Human Glioma Cells

A Natural Degradant of Curcumin, Feruloylacetone Inhibits Cell Proliferation via Inducing Cell Cycle Arrest and a Mitochondrial Apoptotic Pathway in HCT116 Colon Cancer Cells

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