Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines

Al-Fatlawi, Anees Abbas; Al-Fatlawi, Atheer Abbas; Irshad, Muhammad; Uddin, Rahis; Ahmad, Ayaz

doi:10.3109/13880209.2014.911919

Cited by 37 publications

(22 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding underlines the importance of neutrophils in promoting HPV‐induced carcinogenesis, as previously observed in a similar animal model (Pahler et al, ). These findings agree with previous in vitro studies using parthenolide (Al‐Fatlawi et al, ; Mendonca et al, ; Wu et al, ). Considering the promising results obtained in previous studies, with lung and prostate cancer (Deraska et al, ; Estabrook et al, ; Morel et al, ), it would now be interesting to study the ability of DMAPT to enhance the in vivo efficacy of radiation therapy and of DNA‐damaging chemotherapeutic agents (e.g., platinum‐based drugs like cisplatin) in the same, or in a similar in vivo animal model.…”

Section: Discussionsupporting

confidence: 93%

“…Parthenolide was able to inhibit the growth of HPV16‐transformed SiHa cells in vitro (Wu et al, ). More recently, Al‐Fatlawi et al reported that parthenolide inhibited the growth of SiHa (HPV16‐transformed) cells with an IC50 of 8.42 μM (Al‐Fatlawi et al, ). The authors confirmed that parthenolide upregulated Bax while downregulating Bcl‐2, thus inducing apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…In skeletal muscle, DMAPT was shown to prevent cancer cachexia by modulating the Pax7-Pgc-1β axis (Wang et al, 2017). Parthenolide has shown efficacy against HPV-transformed cell lines in vitro (Al-Fatlawi, Al-Fatlawi, Irshad, Rahisuddin, & Ahmad, 2015;Mendonca et al, 2007;Wu et al, 2006) but in vivo tests of parthenolide or DMAPT against-HPV-induced lesions are still missing.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Santos

Moreira‐Pais

Neto

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

The nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) has been implicated in the progression of cancers induced by high‐risk human papillomaviruses (HPV). In cancer patients, NF‐κB is also thought to drive a chronic systemic inflammatory status, leading to cachexia. This study addressed the ability of dimethylaminoparthenolide (DMAPT), a water‐soluble NF‐κB inhibitor, to block the development of HPV‐induced lesions and wasting syndrome in HPV16‐transgenic mice. Mice received DMAPT orally (100 mg/kg/day), once a day, for 6 consecutive weeks. Body weight was monitored weekly along with food and water intake. After 6 weeks the animals were submitted to a grip strength test and sacrificed for specimen collection. Skin samples were analyzed histologically and for expression of NF‐κB‐regulated genes Bcl2 and Bcl2l1. Gastrocnemius muscles were weighted and analyzed for expression of NF‐κB subunits p50, p52, p65, and Rel‐B. DMAPT reduced the incidence of epidermal dysplasia (18.2% versus 33.3% in HPV16+/− untreated mice). This was associated with reduced expression of Bcl2 and Bcl2l1 (p = .0003 and p = .0014, respectively) and reduced neutrophilic infiltration (p = .0339). Treated mice also showed partially preserved bodyweight and strength, which were independent of the expression levels of NF‐κB subunits in skeletal muscle.These results suggest that NF‐κB inhibition may be a valid strategy against HPV‐induced lesions in vivo and warrant further preclinical tests particularly in the set of combination therapies. In addition, the data may support the use of DMAPT to prevent wasting syndrome.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Santos

Moreira‐Pais

Neto

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…Activation of the extrinsic pathway can promote interactions with intermediates, leading to mitochondrial stress and resulting in the activation of the intrinsic cell death pathway [16]. Parthenolide also induced apoptosis in neoplastic cells by upregulating Bax and caspase-3 expression [18], thus corroborating our findings. Death by apoptosis can also be evidenced by damage of cellular DNA, which becomes fragmented and condensed, as well as by morphological changes in the cellular nucleus [19].…”

Section: Effect Of Parthenolide On Caspase-8 and Caspase-9 Expressionsupporting

confidence: 80%

Parthenolide Influences Herpes simplex virus 1 Replication in vitro

et al. 2018

View full text Add to dashboard Cite

Background/Aims: Parthenolide is a sesquiterpene lactone that is present in plants of the Tanacetum genus, for which many biological effects have already been reported, including antiherpetic activity. Although the effectiveness of parthenolide against Herpes simplex virus 1 (HSV-1) has already been demonstrated, such findings are still controversial. The objective of this study was to investigate the ways in which parthenolide exerts anti-HSV-1 activity. Methods: The cytotoxicity and antiviral activity of parthenolide were determined by the MTT method and plaque reduction assay, respectively. The expression of cell and viral proteins during the treatment of infected cells was investigated by Western blot. Results: Both strains of HSV-1 were sensitive to parthenolide, and parthenolide was active only after penetration of the virus into the host cell. The expression of p65 protein decreased, the expression of caspases 8 and 9 increased, and the expression of c-Jun N-terminal kinase (JNK) and p38 protein was altered in infected cells after parthenolide treatment, resulting in lower cell survival. The low expression of viral proteins gB, gD, and ICP0 confirmed the reduction of HSV-1 particle production. Conclusion: Parthenolide exerts anti-HSV-1 activity by impairing cell viability, which consequently interferes with the efficient infection and production of new viral particles.

show abstract

“…It has additionally been demonstrated to have the potential to treat certain types of cancer, including leukemia, and hepatic and breast cancer (21)(22)(23)(24). Parthenolide is able to regulate multiple cellular and molecular signals in order to induce tumor cell apoptosis (25). It may additionally regulate the expression of the apoptosis regulator Bcl-2 (Bcl-2) protein family and caspases (25), and promote the loss of mitochondrial function (26).…”

Section: Introductionmentioning

confidence: 99%

Parthenolide inhibits hydrogen peroxide‑induced osteoblast apoptosis

Mao

Zhu

2018

Mol Med Report

View full text Add to dashboard Cite

Parthenolide is a natural product from the shoots of Tanacetum parthenium that has been demonstrated to have immunomodulatory effects in a number of diseases. The present study aimed to determine the effect and mechanism of parthenolide on the apoptotic ability of H2O2‑induced osteoblasts. Cell viability was analyzed with a MTT assay and the apoptotic rate was subsequently measured using flow cytometry. The activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX), and the serum marker enzymes alkaline phosphatase (ALP), malondialdehyde (MDA) and lactate dehydrogenase (LDH) was measured. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were performed to analyze the expression levels of osteogenesis and oxidative stress‑associated genes. The results indicated that parthenolide increased cell viability and inhibited the apoptosis of H2O2‑induced osteoblasts. Parthenolide decreased the levels of reactive oxygen species, MDA, LDH and ALP. SOD and GPX levels were increased by parthenolide in H2O2‑induced osteoblasts. This suggested that parthenolide may break the equilibrium state of oxidative stress and inhibit cellular apoptosis. Parthenolide additionally increased the expression levels of oxidative stress‑associated genes, including nuclear factor erythroid 2 like 2, hemeoxygenase‑1 and quinone oxidoreductase 1 in H2O2‑induced osteoblasts. Furthermore, parthenolide increased the expression of osteogenesis‑associated genes, including runt‑related transcription factor 2, osteopontin, osteocalcin and collagen 1 in H2O2‑inducedosteoblasts. Therefore, it was concluded that parthenolide may be used in the treatment of osteoporosis.

show abstract

Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines

Cited by 37 publications

References 38 publications

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Parthenolide Influences <b><i>Herpes simplex</i></b> v<b><i>irus 1</i></b> Replication in vitro

Parthenolide inhibits hydrogen peroxide‑induced osteoblast apoptosis

Contact Info

Product

Resources

About