The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress

Hr, Jin; Zhao, Jiong; Zhang, Z; Liao, Yang; Wang, CZ; Huang, Wei‐Hua; Li, SP; He, Tong‐Chuan; Yuan, Cai; Du, Wei

doi:10.1038/cddis.2012.122

Cited by 67 publications

(65 citation statements)

References 40 publications

(51 reference statements)

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“…The anticancer effect of FAD has recently been reported. Jin et al reported that FAD induces cell death in colorectal cancer cells, and also suggested that the similar effect and mechanisms in several cancer cells derived from different tissues [12]. In our study, we further demonstrated the anticancer effects and related mechanisms of FAD in multiple breast cancer cell lines in details.…”

Section: Discussionsupporting

confidence: 77%

Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress

Lü

Zhao

et al. 2017

PLoS ONE

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Falcarindiol (FAD) is a natural polyyne have been found in many food and dietary plants. It has been found to have various beneficial biological activities. In this study, we demonstrated its anticancer function and mechanism in breast cancer cells. We found that FAD preferentially induces cell death in breast cancer cells. FAD-induced cell death is caspase-dependent. However, FAD induces autophagy to contribute to the cell death. Blocking autophagy by either chemical inhibitors or genetic knockout of autophagy signaling component inhibits FAD-induced cell death. We further found that FAD-induced cell death is mediated by the induction of endoplasmic reticulum stress. We also identified that FAD has synergistic effect with approved cancer drugs 5-FU and Bortezomib in killing breast cancer cells. Summarily, these data demonstrate that FAD has strong and specific anticancer effect in breast cancer cells, and provide some insights about the roles of autophagy in FAD-induced cell death.

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Section: Discussionsupporting

confidence: 77%

Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress

Lü

Zhao

et al. 2017

PLoS ONE

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“…Our results were consistent with previous studies showing that the ER chaperone GRP78 expression contributes to in vitro and in vivo antiapoptotic effects and chemotherapy resistance in many cancers (Booth et al 2012;Chang et al 2012;Hardy et al 2012;Jin et al 2012;Lee 2007). For example, levels of GRP78 in human gastric cancer cells are strongly correlated with taxane-based therapeutic resistance and recurrence of the disease (Yang et al 2014).…”

Section: Discussionsupporting

confidence: 92%

GRP78 regulates sensitivity of human colorectal cancer cells to DNA targeting agents

et al. 2014

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This study was carried out to investigate the activation status of unfolded protein response (UPR) in colorectal cancer (CRC) and its contribution to CRC resistance to chemotherapy-induced apoptosis. Chemotherapy-induced apoptosis was assessed by the propidium iodide method. Activation of UPR was evaluated in CRC cell lines using immunoblotting technique and in CRC tissues using immunohistochemistry. Findings of the present study revealed that the UPR is constitutively activated in CRC cell lines and CRC tissues isolated from patients, as evidenced by relatively high levels of the 78-kDa glucose-regulated protein (GRP78) and spliced X-box-binding protein 1 mRNA in tissue samples. In addition, CRC cell lines differentially responded to clinically relevant DNA-targeting agents including cisplatin, and 5-flourouracil. Moreover, the levels of GRP78 were inversely associated with sensitivity of CRC cells to chemotherapy-induced apoptosis. Inhibition of GRP78 by siRNA resulted in increased sensitivity of CRC cells to chemotherapeutic agents. Collectively, current results appear to provide novel insights into the role of UPR in determining sensitivity of CRC cells to chemotherapeutic agents and might have important implications for personalized CRC treatment.

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“…To evaluate if CP effects on proteasome activity lead to ER stress, we evaluated the expression of ER stress marker GRP78, CHOP and the splicing of XBP1 in CP-treated RS4;11 and SEM cells [26,27]. …”

Section: Resultsmentioning

confidence: 99%

A novel copper(I) complex induces ER-stress-mediated apoptosis and sensitizes B-acute lymphoblastic leukemia cells to chemotherapeutic agents

et al. 2014

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A phosphine copper(I) complex [Cu(thp)4][PF6] (CP) was recently identified as an efficient in vitro antitumor agent. In this study, we evaluated the antiproliferative activity of CP in leukemia cell lines finding a significant efficacy, especially against SEM and RS4;11 cells. Immunoblot analysis showed the activation of caspase-12 and caspase-9 and of the two effector caspase-3 and -7, suggesting that cell death occurred in a caspase-dependent manner. Interestingly we did not observe mitochondrial involvement in the process of cell death. Measures on semipurified proteasome from RS4;11 and SEM cell extracts demonstrated that chymotrypsin-, trypsin- and caspase-like activity decreased in the presence of CP. Moreover, we found an accumulation of ubiquitinated proteins and a remarkable increase of ER stress markers: GRP78, CHOP, and the spliced form of XBP1. Accordingly, the protein synthesis inhibitor cycloheximide significantly protected cancer cells from CP-induced cell death, suggesting that protein synthesis machinery was involved. In well agreement with results obtained on stabilized cell lines, CP induced ER-stress and apoptosis also in primary cells from B-acute lymphoblastic leukemia patients. Importantly, we showed that the combination of CP with some chemotherapeutic drugs displayed a good synergy that strongly affected the survival of both RS4;11 and SEM cells.

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The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress

Cited by 67 publications

References 40 publications

Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress

Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress

GRP78 regulates sensitivity of human colorectal cancer cells to DNA targeting agents

A novel copper(I) complex induces ER-stress-mediated apoptosis and sensitizes B-acute lymphoblastic leukemia cells to chemotherapeutic agents

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