A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production

Xie, Zhaoxiong; Zhang, Hanqing; Zhu, Guo‐Qing; Wang, Yu‐Huang; Yu, Xiang; Zhu, Xin-Bo; Liang, Guang; Xiao, Jian; Li, Xiaokun

doi:10.3892/mmr.2011.700

Cited by 18 publications

(12 citation statements)

References 26 publications

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“…The p-eIF2α protein subsequently up-regulates the expression of ATF4 [31]. During ER stress-induced apoptosis, ATF-4 expression can activate pro-apoptotic signalling pathways through initiation of its downstream transcriptional factor CHOP, which subsequently triggers ER stress-specific cascades for the induction of cell apoptosis [32, 33]. Thus, to investigate the possible signalling pathways involved in BP5-induced ER stress-related apoptosis, we screened UPR sensors (IRE-1, PERK and ATF6) as well as their downstream signalling molecules (XBP-1s, eIF2α, ATF4 and CHOP) in HCT116 cells.…”

Section: Discussionmentioning

confidence: 99%

Bursopentin (BP5) induces G1 phase cell cycle arrest and endoplasmic reticulum stress/mitochondria-mediated caspase-dependent apoptosis in human colon cancer HCT116 cells

et al. 2019

Cancer Cell Int

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Background Bursopentin (BP5) is a multifunctional pentapeptide found in the chicken bursa of Fabricius. Recent study indicated that BP5 significantly stimulates expression of p53 protein in colon cancer HCT116 cells. However, the effects and underlying mechanisms of BP5 on HCT116 cell proliferation remain largely unclear. Methods Analyses of cell viability, cell cycle arrest as well as apoptosis were performed to study the actions of BP5 on HCT116 cells. Western blot analyse was assayed to measure the cell cycle-related and apoptosis-related proteins. Specific siRNAs targeting IRE1, ATF-6, and PERK were used for IRE1, ATF-6, and PERK knockdown, respectively. Cellular reactive oxygen species (ROS) were detected using a H 2 DCF-DA green fluorescence probe. Cytosolic free Ca 2+ concentrations and mitochondrial membrane potential (ΔΨm) were measured using Fluo-3 AM and JC-1 stains, respectively. Results BP5 possessed strong inhibitory effects on the cell growth and induced apoptosis in HCT116 cells. Mechanistically, BP5 arrested the cell cycle at G1 phase by increasing p53 and p21 expression and decreasing cyclin E1-CDK2 complex expression. BP5 treatment dramatically activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway, as revealed by the significantly enhanced expression of unfolded protein response (UPR) sensors (IRE1α, ATF6, PERK) as well as downstream signaling molecules (XBP-1s, eIF2α, ATF4 and CHOP), and by the significantly altered the BP5-induced phenotypic changes in IRE1, ATF6, and PERK knockdown cells. Additionally, BP5-induced ER stress was accompanied by the accumulation of cytosolic free Ca 2+ and intracellular ROS. Furthermore, BP5 treatment resulted in the increase of Bax expression, the decrease of Bcl-2 expression and the reduction of ΔΨm, subsequently causing a release of cytochrome c from the mitochondria into the cytoplasm and finally enhancing the activities of caspase-9 and -3. In addition, z-VAD-fmk, a pan-caspase inhibitor, markedly rescued BP5-induced cell viability reduction and reduced BP5-induced apoptosis. Conclusions Our present results suggest that BP5 has an anticancer capacity to arrest cell cycle at G1 phase and to trigger ER stress/mitochondria-mediated caspase-dependent apoptosis in HCT116 cells. Therefore, our findings provide insight into further investigations of the anticancer activities of BP5. Electronic supplementary material The online version of this article (10.1186/s12935-019-0849-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Bursopentin (BP5) induces G1 phase cell cycle arrest and endoplasmic reticulum stress/mitochondria-mediated caspase-dependent apoptosis in human colon cancer HCT116 cells

et al. 2019

Cancer Cell Int

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“…In two different human ovarian cancer cell lines (A2780 and CP70), the curcumin analogue B19 induced apoptosis that was more effective than curcumin in the activation of caspase-3. At an apoptosis-promoting concentration, B19 induced ROS production and ER stress activation; similar to curcumin, B19 acts through different molecular pathways, including ROS and ER stress [66].…”

Section: Natural Compoundsmentioning

confidence: 99%

Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds

Limonta

Moretti

Marzagalli

et al. 2019

IJMS

100

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Cancer represents a serious global health problem, and its incidence and mortality are rapidly growing worldwide. One of the main causes of the failure of an anticancer treatment is the development of drug resistance by cancer cells. Therefore, it is necessary to develop new drugs characterized by better pharmacological and toxicological profiles. Natural compounds can represent an optimal collection of bioactive molecules. Many natural compounds have been proven to possess anticancer effects in different types of tumors, but often the molecular mechanisms associated with their cytotoxicity are not completely understood. The endoplasmic reticulum (ER) is an organelle involved in multiple cellular processes. Alteration of ER homeostasis and its appropriate functioning originates a cascade of signaling events known as ER stress response or unfolded protein response (UPR). The UPR pathways involve three different sensors (protein kinase RNA(PKR)-like ER kinase (PERK), inositol requiring enzyme1α (IRE1) and activating transcription factor 6 (ATF6)) residing on the ER membranes. Although the main purpose of UPR is to restore this organelle’s homeostasis, a persistent UPR can trigger cell death pathways such as apoptosis. There is a growing body of evidence showing that ER stress may play a role in the cytotoxicity of many natural compounds. In this review we present an overview of different plant-derived natural compounds, such as curcumin, resveratrol, green tea polyphenols, tocotrienols, and garcinia derivates, that exert their anticancer activity via ER stress modulation in different human cancers.

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“…Treated cells promoted formation of ubiquitinated misfolded proteins and induced ER stress response [ 73 ]. The accumulation of misfolded proteins in the ER, activated the unfolded protein response (UPR) and ultimately led to autophagy [ 73 , 74 , 75 , 76 ].…”

Section: Curcumin—general Description and Pharmacokineticsmentioning

confidence: 99%

Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

Terlikowska

Witkowska

Zujko

et al. 2014

IJMS

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Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.

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A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production

Cited by 18 publications

References 26 publications

Bursopentin (BP5) induces G1 phase cell cycle arrest and endoplasmic reticulum stress/mitochondria-mediated caspase-dependent apoptosis in human colon cancer HCT116 cells

Bursopentin (BP5) induces G1 phase cell cycle arrest and endoplasmic reticulum stress/mitochondria-mediated caspase-dependent apoptosis in human colon cancer HCT116 cells

Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds

Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

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