Helenalin-induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma

Jang, Ji Hoon; Iqbal, Taha; Min, Kyoung‐jin; Kim, Shin; Park, Jong‐Wook; Son, Eun-Ik; Lee, Tae-Jin; Kwon, Taeg Kyu

doi:10.1016/j.tiv.2012.10.014

Cited by 21 publications

(14 citation statements)

References 38 publications

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“…If applied at its EC 80 concentration of 5 μM, helenalin induced HSP70B' mRNA expression to similar levels as the A. montana extract (Figure 3). The induction of HSP70B' expression by helenalin is consistent with its reported stimulation of apoptosis by the generation of ROS [22]. The results suggest that helenalin is a major active component in the A. montana extract with respect to the observed HSP70B' induction, but further components of the STL or flavonoid fractions may have additive or synergistic roles in A. montana cytotoxicity in HaCaT cells.…”

Section: Resultssupporting

confidence: 83%

A Sensitive Sensor Cell Line for the Detection of Oxidative Stress Responses in Cultured Human Keratinocytes

Hofmann

Priem

Bartzsch

et al. 2014

Sensors

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In the progress of allergic and irritant contact dermatitis, chemicals that cause the generation of reactive oxygen species trigger a heat shock response in keratinocytes. In this study, an optical sensor cell line based on cultured human keratinocytes (HaCaT cells) expressing green fluorescent protein (GFP) under the control of the stress-inducible HSP70B' promoter were constructed. Exposure of HaCaT sensor cells to 25 μM cadmium, a model substance for oxidative stress induction, provoked a 1.7-fold increase in total glutathione and a ∼300-fold induction of transcript level of the gene coding for heat shock protein HSP70B'. An extract of Arnica montana flowers resulted in a strong induction of the HSP70B' gene and a pronounced decrease of total glutathione in keratinocytes. The HSP70B' promoter-based sensor cells conveniently detected cadmium-induced stress using GFP fluorescence as read-out with a limit of detection of 6 μM cadmium. In addition the sensor cells responded to exposure of cells to A. montana extract with induction of GFP fluorescence. Thus, the HaCaT sensor cells provide a means for the automated detection of the compromised redox status of keratinocytes as an early indicator of the development of human skin disorders and could be applied for the prediction of skin irritation in more complex in vitro 3D human skin models and in the development of micro-total analysis systems (μTAS) that may be utilized in dermatology, toxicology, pharmacology and drug screenings.

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Section: Resultssupporting

confidence: 83%

A Sensitive Sensor Cell Line for the Detection of Oxidative Stress Responses in Cultured Human Keratinocytes

Hofmann

Priem

Bartzsch

et al. 2014

Sensors

View full text Add to dashboard Cite

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“…Similarly, here we show that DhL induces cell death, DNA damage, PS exposure and morphological features compatible with programmed cell death in both replicative epimastigote and non-replicative trypomastigote forms of the parasite. Helenalin induces apoptosis in several cancer cell lines such as Caki (human renal clear cell carcinoma), ACHN (human renal carcinoma), HT29 (human colon carcinoma) and HCT116 (human colon carcinoma) via reactive oxygen species (ROS) production (Jang et al 2013). In activated CD4+ T cells, Hln induces cell death by triggering the mitochondrial apoptotic pathway by rapid stabilization of p53, nuclear localization of p53 and AIF, and an increase in ROS production that results in loss of mitochondrial membrane potential (Berges et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: A new therapeutic target?

et al. 2014

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“…Because of chemoresistance (22), many complementary and alternative medicine are investigated in preventing and treating renal cell carcinoma (21,28,29,34). Traditional Chinese medicine is one of them for complementary and alternative therapy.…”

Section: Discussionmentioning

confidence: 99%

<b>Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN </b><b>phosphatase </b>

et al. 2017

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Cordycepin is an active component extracted from Traditional Chinese medical herb Cordyceps militaris. Many reports demonstrated that cordycepin harbors antitumor activity in a broad spectrum of cancer types. In this study the actions and the underneath molecular mechanisms of cordycepin were investigated in renal cell carcinoma Caki-1 cell line. Results showed that cordycepin induced apoptotic cell death and inhibited cell migration in Caki-1 cells. Quantitative real-time PCR results and western blot analyses indicated cordycepin dose-dependently decreased microRNA-21 expression and Akt phosphorylation levels in Caki-1 cells, but increased PTEN phosphatase levels. Block of cordycepin-induced microRNA-21 decrease or PTEN increase in Caki-1 cells by transfection of microRNA-21 mimic or PTEN siRNA significantly attenuated cordycepin-induced cell death and inhibition of cell migration. Taken together, findings in present study suggested that cordycepin induced apoptotic cell death in renal cell carcinoma through regulation of microRNA-21 and PTEN phosphatase. Furthermore, present study also firstly illustrated that cordycepin inhibited cell migration of renal cell carcinoma, which also involved micro-RNA-21 and PTEN phosphatase.Renal cell carcinoma (RCC) is the most lethal urological cancer, accounting for 87% of all renal malignancies and 2-3% of all cancers (4). In the past two decades, the global incidence of RCC has increased by 2% per year (4). Worldwide, the agestandardized incidence and mortality of RCC were 6 per 100,000 and 2.1 per 100,000 respectively (43). Despite advance in diagnostic techniques, up to 20-30% of patients with RCC present with metastasis (4). The prognosis of RCC has historically been poor, with 5-year survival rate of 8% among patients with metastatic RCC (9). Although recent progress about understanding of the pathogenesis of RCC has led to novel immune-based and targeted treatments for this chemoresistant cancer, no one drug obtains overall response rate of 100% and durable complete responses (4, 9). Development of neo-adjuvant therapy is still in a demand at present. Cordycepin is a main active composition extracted from Cordyceps militaris and has been reported to harbor anti-tumor activity in a broad spectrum of cancer types, including lung cancer (50), ovarian cancer (46), leukemia (30), breast cancer (47), and so on (33). Two recent reports firstly demonstrated that cordycepin could induce apoptosis in renal cell carcinoma through Erk-JNK signaling pathway (20,48) and indicated the potential application of cordycepin in treating renal cell carcinoma. However, the actions and the underneath molecular mechanisms of cordycepin in renal cell carcinoma are not definitely clear and warrant extensive and further investigations. Recently, a comprehensive molecular analysis

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Helenalin-induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma

Cited by 21 publications

References 38 publications

A Sensitive Sensor Cell Line for the Detection of Oxidative Stress Responses in Cultured Human Keratinocytes

A Sensitive Sensor Cell Line for the Detection of Oxidative Stress Responses in Cultured Human Keratinocytes

Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: A new therapeutic target?

<b>Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN </b><b>phosphatase </b>

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