Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells

Soares, Nathália da Costa Pereira; Teodoro, Anderson Junger; Oliveira, Felipe Leite de; Santos, Carlos Antônio do Nascimento; Takiya, Christina Maeda; Saback, Oswaldo; Bianco, Mario; Palumbo, Antônio; Nasciutti, Luiz Eurico; Ferreira, Luciana Bueno; Gimba, Etel Rodrigues Pereira; Borojević, Radovan

doi:10.1080/01635581.2013.812225

Cited by 37 publications

(17 citation statements)

References 29 publications

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“…Prostate cancer (PCa), an epitheliogenic malignant tumor in prostate, is the second most common malignancy and one of the major causes for global cancer-related deaths among men, seeing about 29,000 cases in 2013 all over the world [1][2][3][4][5]. The cancer shows no obvious symptoms at early stage, which increases the risk of death among the patients [6,7].…”

Section: Introductionmentioning

confidence: 99%

HOXC6 in the prognosis of prostate cancer

Zhou

Yang

Song

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Aims: Our study aimed to investigate the expression and prognostic role of homeobox C6 (HOXC6) in prostate cancer (PCa). Methods: Relative expression of HOXC6 at mRNA and protein levels in tissues and cell lines of PCa were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. Association between HOXC6 expression and clinical factors was analyzed by Chisquare test. HOXC6 effects on the proliferation, invasion and metastasis of PCa cells were severally examined through CCK-8 and transwell assays. Results: Relative expressions of HOXC6 at mRNA and protein levels were obviously higher in both PCa tissues and cells than in adjacent non-cancerous tissues and normal human prostate epithelial cells (p < .05). Chi-square test demonstrated that high expression of HOXC6 was significantly associated with PSA concentration, Gleason score and TNM stage (p < .05). The down-regulation of HOCX6 remarkably inhibited the proliferation, migration and invasion of PCa cells. Kaplan-Meier analysis showed that patients with high HOXC6 expression had shorter overall survival than those with low HOXC6 expression (log rank test, p < .001). Conclusion: Up-regulated HOXC6, in PCa patients, could not only participate in the progression of PCa but also function as an independent prognostic marker for the cancer.

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Section: Introductionmentioning

confidence: 99%

HOXC6 in the prognosis of prostate cancer

Zhou

Yang

Song

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Considering the potent anticancer activity of lycopene, further studies clarifying the controversial effects of lycopene on the formation of skin cancer would be significant to provide further insights into the mechanisms underlying the regulation of skin cancer progression. There was one thing need to be noted that the cytostatic nature of lycopene may requires a substantial time for the alteration of mRNA or protein to exhibit the ultimate cellular apoptosis, it may cause a negative effect of lycopene on tumorigenesis without enough time for treatment as previously reported [Soares Nda et al, 2013;Takeshima et al, 2014]. Notably, the experimental protocols for cell lines, lycopene dose and vehicle, toxic organic solvents, exposure duration, and UV dose should be standardized in order to obtain comparable results.…”

Section: Discussionmentioning

confidence: 99%

Lycopene Protects Keratinocytes Against UVB Radiation‐Induced Carcinogenesis via Negative Regulation of FOXO3a Through the mTORC2/AKT Signaling Pathway

Chen¹,

Xu²,

2017

J of Cellular Biochemistry

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Lycopene, one of the most potent anti-oxidants, has been reported to exhibit potent anti-proliferative properties in a wide range of cancer cells through modulation of the cell cycle and apoptosis. Forkhead box O3 (FOXO3a) plays a pivotal role in modulating the expression of genes involved in cell death. Herein, we investigated the role of FOXO3a signaling in the anti-cancer effects of lycopene. Results showed that lycopene pretreatment attenuated UVB-induced cell hyper-proliferation and promoted apoptosis, accompanied by decreased cyclindependent kinase 2 (CDK2) and CDK4 complex in both human keratinocytes and SKH-1 hairless mice. FOXO3a is phosphorylated in response to UVB irradiation and sequestered in the cytoplasm, while lycopene pretreatment rescued this sensitization. Gene ablation of FOXO3a attenuated lycopene-induced decrease in cell hyper-proliferation, CDK2, and CDK4 complex, indicating a critical role of FOXO3a in the lycopene-induced anti-proliferative effect of keratinocytes during UVB irradiation. Transfection with FOXO3a siRNA inhibited the lycopene-induced increase in cell apoptosis, BAX and cleaved PARP expression. Moreover, loss of AKT induced further accelerated lycopene-induced FOXO3a dephosphorylation, while loss of mechanistic target of rapamycin complex 2 (mTORC2) by transfection with RICTOR siRNA induced levels of AKT phosphorylation comparable to those obtained with lycopene. In contrast, overexpression of AKT or mTORC2 decreased the effects of lycopene on the expression of FOXO3a as well as AKT phosphorylation, suggesting that lycopene depends on the negative modulation of mTORC2/AKT signaling. Taken together, our findings demonstrate that the mTORC2/AKT/FOXO3a axis plays a critical role in the anti-proliferative and pro-apoptotic effects of lycopene in UVB-induced photocarcinogenesis.

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“…In this study, H/R treatment significantly increased CHOP/GADD153 expression as well as the ratio of Bax to Bcl-2 ( Fig 5 ). Numerous studies have shown that lycopene may exert its protective effect via maintaining the balance of Bax and Bcl-2 in cortical neurons, prostate cancer cells, hepatic tissue and kidney tissue [ 14 , 15 , 42 , 43 ]. Our previous study reported that lycopene strikingly inhibited cytochrome c release and subsequent cell apoptosis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

Chen

et al. 2015

PLoS ONE

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Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes.

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Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells

Cited by 37 publications

References 29 publications

HOXC6 in the prognosis of prostate cancer

HOXC6 in the prognosis of prostate cancer

Lycopene Protects Keratinocytes Against UVB Radiation‐Induced Carcinogenesis via Negative Regulation of FOXO3a Through the mTORC2/AKT Signaling Pathway

Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

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