Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis

Bigdeli, Bahareh; Goliaei, Bahram; Masoudi-Khoram, Nastaran; Jooyan, Najmeh; Nikoofar, Alireza; Rouhani, Maryam; Haghparast, Abbas; Mamashli, Fatemeh

doi:10.1016/j.taap.2016.10.021

Cited by 28 publications

(18 citation statements)

References 60 publications

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“…Estrogen and other hormones, and specific receptor subset levels, may be involved in the reduced radiation sensitivity of tumors in younger women, along with associated elevated DNAdamage repair responses. In this regard, it is interesting that phytoestrogens are being used for combined therapy to decrease the radiation dose delivered to patients and subsequent side effects and improve radiosensitivity, regardless of estrogen receptor status in breast cancer (24).…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry

et al. 2019

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Cervical cancer screening rate is extremely low and the governmental recommendation of HPV vaccine has been suspended for 5 years in Japan. Here, we utilized data from the Osaka Cancer Registry, collected between 1976 and 2012, to evaluate cervical cancer trends in Japan. Age-adjusted incidence, relative survival, and conditional survival rates were calculated using multiple imputation methods and period analyses in 25,826 cervical cancer cases. Association of survival rates and clinical factors, including patients' age, clinical stage, and treatment procedures, were also analyzed. A trend for significantly decreasing age-adjusted incidence of cervical cancer (per 100,000) began in 1976 but reversed after 2000, increasing significantly to date (annual percent change ¼ 3.8, 95% confidence interval, 2.7-4.8; age-adjusted rate: 28.0 in 1976, 9.1 in 2000, 14.1 in 2012). The 10-year relative survival rate improved significantly after 2002, especially in cases of "localized" and "adjacent organs" disease; this was likely due to the introduction of concurrent chemotherapy and radiation. The conditional 5-year relative survival rate improved significantly yearly until the fourth survival year. In the surgery-based group, we observed no age-dependent differences in outcomes. Unexpectedly, however, prognosis for younger age groups was poorer in the radiation-based treatment group. These results indicate that although relative survival rates have recently increased, treatment for more advanced cases with distant metastasis requires further improvement. In addition, this study is the first to suggest that age might be an important predictor of radiotherapy resistance in cervical cancer. Significance: A large-cohort analysis of cervical cancer cases reveals that age-adjusted incidence in Japan has increased since 2000 and that age may negatively correlate with resistance to radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry

et al. 2019

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“…Treatment with ENL and END in vitro has been shown to reduce MDA-MB-231 cell proliferation, adhesion, migration, and invasion [22, 23]. Researchers have also demonstrated that ENL is a radiosensitizer [24] and enhances the cytotoxicity of chemotherapeutic agents [25] in MDA-MB-231 cells. In addition, supplementation with flaxseed oil or SDG in vivo was shown to inhibit metastasis from ERα-negative MDA-MB-435 xenografts [48, 49].…”

Section: Discussionmentioning

confidence: 99%

The flaxseed lignan secoisolariciresinol diglucoside decreases local inflammation, suppresses NFκB signaling, and inhibits mammary tumor growth

Bowers

Lineberger

Ford

et al. 2018

Breast Cancer Res Treat

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Purpose Exposure to the polyphenolic plant lignan secoisolariciresinol diglucoside (SDG) and its metabolite enterolactone (ENL) has been associated with reduced breast cancer progression, particularly for estrogen receptor alpha (ERα)-negative disease, and decreased preclinical mammary tumor growth. However, while preclinical studies have established that SDG and ENL affect measures of progression in models of triple-negative breast cancer (TNBC, a subset of ERα-negative disease), the molecular mechanisms underlying these effects remain unclear. Methods C57BL/6 mice were fed a control diet (control, 10% kcal from fat) or control diet + SDG (SDG, 100 mg/kg diet) for 8 weeks, then orthotopically injected with syngeneic E0771 mammary tumor cells (a model of TNBC); tumor growth was monitored for 3 weeks. The role of reduced NF-κB signaling in SDG’s anti-tumor effects was explored in vitro via treatment with the bioactive SDG metabolite ENL. In addition to the murine E0771 cells, the in vitro studies utilized MDA-MB-231 and MCF-7 cells, two human cell lines which model the triple-negative and luminal A breast cancer subtypes, respectively. Results SDG supplementation in the mice significantly reduced tumor volume and expression of phospho-p65 and NF-κB target genes ( P < 0.05). Markers of macrophage infiltration were decreased in the distal-to-tumor mammary fat pad of mice supplemented with SDG relative to control mice ( P < 0.05). In vitro, ENL treatment inhibited viability, survival, and NF-κB activity and target gene expression in E0771, MDA-MB-231, and MCF-7 cells ( P < 0.05). Overexpression of Rela attenuated ENL’s inhibition of E0771 cell viability and survival. Conclusions SDG reduces tumor growth in the E0771 model of TNBC, likely via a mechanism involving inhibition of NF-κB activity. SDG could serve as a practical and effective adjuvant treatment to reduce recurrence, but greater understanding of its effects is needed to inform the development of more targeted recommendations for its use. Electronic supplementary material The online version of this article (10.1007/s10549-018-5021-6) contains supplementary material, which is available to authorized users.

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“…The cells were incubated in a humidified atmosphere (95%) with 5% CO 2 at 37 °C. MDA-MB-231 and T47D cells were routinely sub-cultured using trypsin/EDTA in phosphate buffered saline (PBS) solution 52 .…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was calculated by comparing absorbance of the treated cells with that of the control cells, which conventionally was 100%. The results were presented as means of three independent experiments 52 .…”

Section: Methodsmentioning

confidence: 99%

A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier

Delavari

Mamashli

Bigdeli

et al. 2018

Sci Rep

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Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make α-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess α-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between α-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M−1) value for the interaction of α-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of α-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in α-Lac’s interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in α-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between α-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that α-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.

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Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis

Cited by 28 publications

References 60 publications

Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry

Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry

The flaxseed lignan secoisolariciresinol diglucoside decreases local inflammation, suppresses NFκB signaling, and inhibits mammary tumor growth

A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier

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