3,5-Dimethyl-&lt;sup&gt;7&lt;/sup&gt;H-Furo[3,2-g]Chromen-7-One as a Potential Anticancer Drug by Inducing p53-Dependent Apoptosis in Human Hepatoma HepG2 Cells

Sun, Jian; Chen, Chaoyue; Luo, Ke; Yeung, Ching‐Hei; Tsang, Tsun Yee; Huang, Zhi Zhen; Wu, Ping; Fung, Kwok‐Pui; Kwok, Tim Tak; Liu, Fei Yan

doi:10.1159/000326915

Cited by 19 publications

(18 citation statements)

References 72 publications

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“…In particular, NF-κB appears to be responsible for the activation of genes involved in proliferation and tumor survival, such as those of the apoptotic proteins Bcl-2 and Bcl-xL (50,51). The results of the present study indicated that PT is essential for AOM/DSS-induced colon cancer carcinogenesis via the apoptotic route-associated Bcl-2 family members, which cause inhibition of NF-κB activation.…”

Section: Discussionmentioning

confidence: 52%

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

et al. 2015

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Abstract. Recently, the nuclear factor (NF)-κB inhibitor parthenolide (PT) was identified as a promising anticancer agent for the promotion of cancer cell apoptosis. Additionally, our previous study demonstrated that PT administration suppresses tumor growth in a xenograft model of colorectal cancer cells via regulation of the B-cell lymphoma-2 (Bcl-2) family. However, the role of PT in the development of colitis-associated colon cancer (CAC) is poorly understood. Therefore, the aim of the present study was to investigate the effects of PT administration on CAC using a murine model. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were administered to induce experimental CAC in the following three groups of treated mice: i) AOM and DSS plus vehicle; ii) AOM, DSS and 2 mg/kg PT; and iii) AOM, DSS and 4 mg/kg PT. It was demonstrated that the histological acuteness of AOM/DSS-induced CAC was significantly reduced following the administration of PT, resulting in decreased NF-κB p65 expression levels via a blockade of phosphorylation and subsequent degradation of inhibitor of κB-α (IκBα). Furthermore, PT administration appeared to enhance the process of carcinogenesis via the downregulation of the antiapoptotic proteins Bcl-2 and Bcl-extra large, mediated by inhibition of NF-κB activation. Apoptosis and caspase-3 expression were markedly increased in the PT-treated group. These findings indicate that PT inhibits IκBα phosphorylation and NF-κB activation, resulting in the initiation of apoptosis and the eventual suppression of CAC development. The beneficial effects of PT treatment observed in the experimental CAC model indicate the potential chemopreventive and therapeutic role of PT in CAC.

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Section: Discussionmentioning

confidence: 52%

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

et al. 2015

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“…On the other hand, it is well known that NF-кB is responsible for the activation of genes involved in proliferation and tumor survival, such as the apoptotic proteins Bcl-2 and Bcl-XL [61,62]. In fact, this transcription factor has been found to be overactivated in many tumors [63-65].…”

Section: Discussionmentioning

confidence: 99%

Sensitization of U937 leukemia cells to doxorubicin by the MG132 proteasome inhibitor induces an increase in apoptosis by suppressing NF-kappa B and mitochondrial membrane potential loss

et al. 2014

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BackgroundThe resistance of cancerous cells to chemotherapy remains the main limitation for cancer treatment at present. Doxorubicin (DOX) is a potent antitumor drug that activates the ubiquitin-proteasome system, but unfortunately it also activates the Nuclear factor kappa B (NF-кB) pathway leading to the promotion of tumor cell survival. MG132 is a drug that inhibits I kappa B degradation by the proteasome-avoiding activation of NF-кB. In this work, we studied the sensitizing effect of the MG132 proteasome inhibitor on the antitumor activity of DOX.MethodsU937 human leukemia cells were treated with MG132, DOX, or both drugs. We evaluated proliferation, viability, apoptosis, caspase-3, -8, and −9 activity and cleavage, cytochrome c release, mitochondrial membrane potential, the Bcl-2 and Bcl-XL antiapoptotic proteins, senescence, p65 phosphorylation, and pro- and antiapoptotic genes.ResultsThe greatest apoptosis percentage in U937 cells was obtained with a combination of MG132 + DOX. Likewise, employing both drugs, we observed a decrease in tumor cell proliferation and important caspase-3 activation, as well as mitochondrial membrane potential loss. Therefore, MG132 decreases senescence, p65 phosphorylation, and the DOX-induced Bcl-2 antiapoptotic protein. The MG132 + DOX treatment induced upregulation of proapoptotic genes BAX, DIABLO, NOXA, DR4, and FAS. It also induced downregulation of the antiapoptotic genes BCL-XL and SURVIVIN.ConclusionMG132 sensitizes U937 leukemia cells to DOX-induced apoptosis, increasing its anti-leukemic effectiveness.

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“…Moreover, 5 patients had severe myelotoxicity which necessitated a reduction in the number of cycles [12]. In a study by Martin et al [13], 400 mg/m 2 carboplatin was administered to 34 untreated patients with MBC every 4 weeks. The RR was 35% (1 CR and 11 PRs).…”

Section: Experience With Single-agent Therapymentioning

confidence: 99%

“…Toxicities were mild and included thrombocytopenia, leukopenia and nausea/vomiting. Only 1 patient developed grade IV thrombocytopenia without overt bleeding [13]. Another study enrolled 40 patients with MBC (13 previously treated and 27 untreated patients) to receive carboplatin doses adjusted for glomerular filtration rate using the Calvert formula.…”

Section: Experience With Single-agent Therapymentioning

confidence: 99%

Anticancer Effects of Imperatorin Isolated from Angelica dahurica: Induction of Apoptosis in HepG2 Cells through both Death-Receptor- and Mitochondria-Mediated Pathways

Luo¹,

Sun²,

Chan³

et al. 2011

Chemotherapy

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Background: Imperatorin (IM) is a furanocoumarin isolated from the root of Angelica dahurica, which is reported to have anticonvulsant and anticancer effects. In this study, the antiproliferative effect of IM on 9 human cancer cell lines was examined, and human hepatoma HepG2 cells were chosen as the target for preferential killing by IM. Particularly, the mechanism of IM-induced apoptosis and in vivo animal effects were also studied. Methods: Cell viability was measured using MTT assay, and apoptosis was detected by Hoechst staining, annexin V-PI staining, and DNA laddering assay. Mitochondrial membrane potential was detected by JC-1 staining. Western blot analysis was employed to detect the expression of apoptosis-related proteins. In addition, the in vivo anticancer effect of IM was examined in nude mice bearing HepG2 cells. Results: IM inhibited the proliferation of HepG2 cells through apoptosis induction in a time- and dose-dependent manner by observation of the nuclear morphology, DNA fragmentation, phosphatidylserine externalization, loss of mitochondrial membrane potential, release of cytochrome c into cytosol, and activation of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase cleavage. As cell death could partly be prevented by the caspase-8 or caspase-9 inhibitor and was evidenced by the results of Western blot analysis, our results also suggest that IM-induced apoptosis is mediated through both death receptor and mitochondrial pathways. In the animal model, IM was found to effectively suppress tumor growth by 31.93 and 63.18% at dosages of 50 and 100 mg/kg, respectively, after treatment for 14 days. No significant weight loss or toxicity to the hosts was found. Conclusions: IM can function as a cancer suppressor by inducing apoptosis in HepG2 cells through both death-receptor- and mitochondria-mediated pathways. Furthermore, the in vivo antitumor activities of IM are significant with negligible weight loss and damage to the host.

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3,5-Dimethyl-<sup>7</sup>H-Furo[3,2-g]Chromen-7-One as a Potential Anticancer Drug by Inducing p53-Dependent Apoptosis in Human Hepatoma HepG2 Cells

Cited by 19 publications

References 72 publications

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling

Sensitization of U937 leukemia cells to doxorubicin by the MG132 proteasome inhibitor induces an increase in apoptosis by suppressing NF-kappa B and mitochondrial membrane potential loss

Anticancer Effects of Imperatorin Isolated from Angelica dahurica: Induction of Apoptosis in HepG2 Cells through both Death-Receptor- and Mitochondria-Mediated Pathways

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