Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells

Ibrahim, Amel B.; Zaki, Hala F.; Ibrahim, Walaa; Omran, Mervat M.; Shouman, Samia A.

doi:10.1016/j.toxrep.2019.10.016

Cited by 20 publications

(18 citation statements)

References 62 publications

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“…These findings clearly suggest that the cell membrane integrity was severely compromised by PtNPs and RA. For example, when T47D cells were exposed to tamoxifen and simvastatin combination, the leakage of LDH was significantly higher than that observed with the control treatment [62]. We have previously reported that treatment with the combination of silver nanoparticles and histone deacetylase inhibitors significantly increases the leakage of LDH, compared with that on individual treatment of human alveolar basal epithelial cells [63].…”

Section: Combination Of Ptnps and Ra Induces Lactate Dehydrogenase (Lmentioning

confidence: 85%

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

Gurunathan

Jeyaraj

Kang

et al. 2020

IJMS

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Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

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Section: Combination Of Ptnps and Ra Induces Lactate Dehydrogenase (Lmentioning

confidence: 85%

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

Gurunathan

Jeyaraj

Kang

et al. 2020

IJMS

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“…The importance of this interaction is intensified as atorvastatin may be prescribed with tamoxifen for cancer patients because of hypercholesterolemia. Apart from their lipid-lowering effects, statins have induced anticancer activity in different cancer cell lines (Ibrahim et al, 2019;Tutuska et al, 2020). Therefore, it is necessary to reduce the dose of tamoxifen in these patients due to synergistic drug interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings are somewhat similar to other cancer types studies of statins therapy. For example, Ibrahim and colleagues (Ibrahim et al, 2019) reported that the simvastatin in combination of tamoxifen increased the apoptotic and necrotic cell death in breast cancer cells. Recently, Stine et al (2016) have shown that simvastatin may have therapeutic benefit for ovarian cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that RhoA family and their down-stream targets are essential for the regulation of G1/S transition in the cell cycle (Noguchi et al, 1998;Villalonga et al, 2006). Synergistic interaction of atorvastatin and tamoxifen may be due to the increase in apoptotic cell death in addition to other mechanisms such as decrease in ROS levels and free radical production (Ibrahim et al, 2019). Liang et al (2017) have provided evidence that the simvastatin in combination with tamoxifen induced DNA damage, apoptosis and inhibited the growth of tamoxifen-resistant cell lines.…”

Section: Discussionmentioning

confidence: 99%

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Atorvastatin enhances the antitumor activity of tamoxifen in B16f10 mouse melanoma cell lines

et al. 2020

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Introduction: Tamoxifen has been used in the treatment of metastatic malignant melanoma more common with other agents in the combined therapy. Up-regulated activity of the mevalonate pathway has been shown in a range of different cancers. Atorvastatin is the most commonly used statin approved for cholesterol reduction by inhibiting the mevalonate pathway and has been shown to inhibit tumor growth. In the present study, we used atorvastatin and tamoxifen combination therapy on B16f10 mouse melanoma cell lines to study whether atorvastatin could increase the sensitivity of melanoma cells to the chemotherapeutic agent such as tamoxifen. Methods: The cell line was treated with different concentrations of tamoxifen and/or atorvastatin for 24 and 48h and the effects of treatment on p53 and RhoA were investigated using quantitative RT-PCR. Results: The combination of atorvastatin and tamoxifen resulted in a potentiation antitumor effect via up-regulation of p53 and down-regulation of RhoA expression against melanoma tumors in vitro. Furthermore, we demonstrated the combination of atorvastatin with tamoxifen could reduce tamoxifen dose to minimize possible detrimental side effects in melanoma. Conclusion: Our results suggested that atorvastatin as a combined therapy with tamoxifen may provide a new approach for improving the efficacy and treating against melanoma cancer but needs further exploration in clinical trials.

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“…Simvastatin + tamoxifenIn vitro and in vivo 1-An increase in the apoptotic and necrotic cell death 2-A decrease in VEGF and MMP-2/-9[252] Fluvastatin + vorinostatIn vitro and in vivo1-A robust apoptosis induction and inhibiting cancer growth 2-Enhancing vorinostat-induced histone acetylation 3-Inducing ER stress 4-Inhibiting the mTOR pathway and AMPK activation Synergistically suppression of the cell proliferation through sub-G1 and S-phase cell cycle arrest 2…”

mentioning

confidence: 99%

Effects of statins on brain tumors: a review

Afshari

Mollazadeh

Henney

et al. 2021

Seminars in Cancer Biology

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Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells

Abstract: Graphical abstract

Cited by 20 publications

References 62 publications

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

Atorvastatin enhances the antitumor activity of tamoxifen in B16f10 mouse melanoma cell lines

Effects of statins on brain tumors: a review

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