Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells

Zhang, Li; Cheng, Xian; Gao, Yanyan; Bao, Jiandong; Guan, Haixia; Lu, Rongrong; Yu, Huixin; Xu, Qiang; Sun, Yang

doi:10.1039/c5fo00681c

Cited by 54 publications

(29 citation statements)

References 32 publications

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“…As shown above, SMG potentiated the effect of H 2 O 2 on DNA damage in MES cells, and DNA damage leads to apoptosis (Zhang et al 2016). Previously we observed that SMG itself was unable to induce apoptosis in wild-type MES cells (Li et al 2015).…”

Section: Resultsmentioning

confidence: 80%

Simulated microgravity potentiates generation of reactive oxygen species in cells

Ran

Fan

et al. 2016

Biophys Rep

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Microgravity (MG) and space radiation are two major environmental factors of space environment. Ionizing radiation generates reactive oxygen species (ROS) which plays a key role in radiation-induced DNA damage. Interestingly, simulated microgravity (SMG) also increases ROS production in various cell types. Thus, it is important to detect whether SMG could potentiate ROS production induced by genotoxins including radiation, especially at a minimal level not sufficient to induce detectable ROS. In this study, we treated mouse embryonic stem (MES) cells with H2O2 and SMG for 24 h. The concentration of H2O2 used was within 30 μmol/L at which intracellular ROS was the same as that in untreated cells. Exposure of cells to SMG for 24 h did not induce significantly higher levels of intracellular ROS than that of control cells either. Simultaneous exposure of cells to both SMG- and H2O2-induced ROS and apoptosis in MES cells. Although incubation in medium containing 5 or 30 μmol/L H2O2 induced a small enhancement of DNA double-strand breaks (DSBs), the addition of SMG treatment dramatically increased DSB levels. Taken together, SMG can significantly potentiate the effects of H2O2 at a low concentration that induce a small or negligible change in cells on ROS, apoptosis, and DNA damage. The results were discussed in relation to the combined effects of space radiation and MG on human body in this study.

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Section: Resultsmentioning

confidence: 80%

Simulated microgravity potentiates generation of reactive oxygen species in cells

Ran

Fan

et al. 2016

Biophys Rep

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“…Oxidative stress plays an important role in controlling cancer cell behavior, and high levels of ROS increase cancer cell apoptosis [14, 15]. We examined whether increased ROS was required for reduced cell viability and increased apoptosis of LoVo and HT-29 cells with curcumin and/or irinotecan treatment.…”

Section: Resultsmentioning

confidence: 99%

Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway

et al. 2017

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Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

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“… 2015 ) and curcumin (Zhang et al. 2016 ), have shown anticancer potential through mitochondrial mechanisms whether associated or otherwise to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

Benfica

Ávila

Rodrigues

et al. 2017

Pharmaceutical Biology

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Context: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells.Objectives: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells.Materials and methods: Cytotoxicity of 4-NRC (4.17–534.5 μM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis.Results: IC50 values obtained were 11.40, 27.31, 15.93 and 15.70 μM for lymphocytes, K562, HL-60 and Jurkat cells, respectively. In K562 cells, 4-NRC (27 μM) promoted apoptosis as verified by cellular morphological changes, a significant increase in PS externalization and sub-G1 cells. Moreover, it significantly arrested the cells at the G0/G1 phase due to a reduction in cyclin D1 expression. These effects of 4-NRC also significantly promoted a reduction in mitochondrial activity and membrane depolarization, accumulation of cytosolic cytochrome c and ROS overproduction. Additionally, it triggered an increase in caspases -3/7, -8 and -9 activities. When the cells were pretreated with N-acetyl-l-cysteine ROS scavenger, 4-NRC-induced apoptosis was partially blocked, which suggests that it exerts cytotoxicity though not exclusively through ROS-mediated mechanisms.Discussion and conclusion: 4-NRC has antileukemic properties, inducing apoptosis mediated by mitochondrial-dependent mechanisms with cyclin D1 inhibition. Given that emerging treatment concepts include novel combinations of well-known agents, 4-NRC could offer a promising alternative for chemotherapeutic combinations to maximize tumour suppression.

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Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells

Cited by 54 publications

References 32 publications

Simulated microgravity potentiates generation of reactive oxygen species in cells

Simulated microgravity potentiates generation of reactive oxygen species in cells

Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

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