Anti‐proliferative and apoptosis‐inducing activity of lycopene against three subtypes of human breast cancer cell lines

Takeshima, Mikako; Ono, Misaki; Higuchi, Takako; Chen, Chen; Hara, Takayuki; Nakano, Susumu

doi:10.1111/cas.12349

Cited by 114 publications

(54 citation statements)

References 39 publications

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“…Flow cytometry assay showed that lycopene induced the apoptosis of MCF-7 cells in a dose-and time-dependent manner, indicating that lycopene inhibited cell proliferation by inducing MCF-7 cell apoptosis. The results of our study were consistent with those of previous studies, which showed that lycopene can arrest cells at G0/G1 phase to inhibit MCF-7 cell proliferation (Takeshima et al, 2014) and induce apoptosis (Teodoro et al, 2012), and provided further evidences on the anti-tumor effects of lycopene on ER (+) breast cancer.…”

Section: Discussionsupporting

confidence: 92%

“…Bax is also a downstream effector of early p53 response gene (Brady and Gil-Gómez, 1998). A previous study showed cell cycle arrest by lycopene (Takeshima et al, 2014). Given the contradicting results obtained from previous studies, the exact role of lycopene in MCF-7 cells, which is an ER (+) breast cancer cell line, remains poorly understood.…”

Section: Introductionmentioning

confidence: 93%

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In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells

Peng¹,

Li²,

Zhou³

et al. 2017

Genet. Mol. Res.

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Breast cancer adversely affects the health status of women; therefore, the prevention and treatment of breast cancer is of critical importance. Lycopene is known to possess several biological effects such as removal of free radicals, alleviation of biological oxidative injury, and inhibition of tumor growth. In this study, we aimed to illustrate the effect of lycopene on tumor cell proliferation and modulation of cancer progression as well as its possible underlying mechanisms in human breast carcinoma cell line MCF-7 in vitro. MCF-7 cells were treated with different lycopene concentrations for 24, 48, and 72 h. Light field microscopy was used to observe cell morphology. MTT assay was used to determine the effect of lycopene on MCF-7 proliferation. Flow cytometry was employed to evaluate cell apoptosis. Real-time quantitative polymerase chain reaction was performed to detect the expression of p53 and Bax. Under microscopic examination, the untreated MCF-7 cells appeared to have a diamond or polygonal shape. Lycopene treatment resulted in cell shrinkage and breakage, whose severity increased in a dose and duration dependent manner. In addition, reduced cell proliferation and increased apoptosis (P < 0.05) were observed using MTT assay and flow cytometry, respectively. Moreover, lycopene could also upregulate the expression of p53 and Bax mRNAs in MCF-7 cells. In conclusion, lycopene inhibits proliferation and facilitates apoptosis of MCF-7 cells in vitro, possibly by regulating the expression of p53 and Bax.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 93%

In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells

Peng¹,

Li²,

Zhou³

et al. 2017

Genet. Mol. Res.

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“…Lycopene, as a chemopreventive candidate for a variety of cancers, has been increasingly reported to induce prolonged anticancer effects. The anti-tumor capacity of lycopene has been found in wide range of cancer cells of different organs and induced carcinogenesis in animal models, including breast cancer cells [Takeshima et al, 2014], prostate cancer cells [Assar et al, 2016;Graff et al, 2016], Renal cell carcinoma [Sahin et al, 2015], hepatocarcinogenesis [Sahin et al, 2014], etc. whether it has anti-cancer effects on skin cancer during UVB exposure, especially the molecular mechanisms underlying those effects are yet not clearly investigated.…”

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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“…Lycopene is a 40-carbon aliphatic chain containing thirteen trans-double bonds, eleven of which are conjugated [72]. Lycopene treatment for seven consecutive days induced strong and sustained activation of the ERK1/2 with downstream cyclin D1 suppression and p21 upregulation [74].…”

Section: Anti-cancer Effects Of Phytochemicals Using Mcf-7 Cell Linementioning

confidence: 99%

Oxidative Stress and Carcinogenesis: Potential of Phytochemicals in Breast Cancer Therapy

Forcados

James

Sallau

et al. 2017

Nutrition and Cancer

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Breast cancer remains a burden in both developed and developing countries, with higher mortality in developing countries. Attempts to eradicate cancer have not been successful despite the progress made in the development of more novel chemotherapeutic drugs. Reactive-oxygen-species-mediated oxidative stress is known to play a role in breast cancer pathogenesis via genetic and epigenetic modifications, resulting in uncontrolled cell proliferation. Phytochemicals could provide leads for the development of alternative therapeutic agents due to their antioxidant activity, as well as their ability to induce apoptosis in cancer cells. However, most of the studies carried out using in vitro models do not continue with further studies in estrogen-receptor-positive in vivo breast cancer models, or fail to examine the possible biochemical mechanisms of phytochemical-based amelioration. This review examines oxidative-stress-mediated carcinogenesis and the potential of phytochemicals as anticancer agents.

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Anti‐proliferative and apoptosis‐inducing activity of lycopene against three subtypes of human breast cancer cell lines

Cited by 114 publications

References 39 publications

In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells

In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells

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

Oxidative Stress and Carcinogenesis: Potential of Phytochemicals in Breast Cancer Therapy

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