Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

Chen, Yuan; Lien, Hsiu-Man; Kao, Min-Chuan; Lo, U‐Ging; Lin, Li-Chiung; Lin, Ching-Yu; Chang, Sheau-Jiun; Chen, Chia-Chang; Hsieh, Jer‐Tsong; H, Lin; Tang, Chih‐Hsin; Lai, Chih‐Ho

doi:10.1371/journal.pone.0169204

Cited by 38 publications

(23 citation statements)

References 52 publications

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“…While further studies are required to understand the underlying mechanisms, these differential effects could be related to a possible drug interaction or synergistic effect on bone tissue with the combination treatment of resveratrol and MTX. This is also consistent with a recent study which showed a synergistic effect of resveratrol combined with radiation in killing the radioresistant prostate cancers in vitro and in enhancing radiation therapy of the mouse model of prostate cancer cell xenograft tumour [39]. Furthermore, our observations of the harmful effect at 10 mg/kg and yet the protective effect on bone at 1 mg/kg of resveratrol in this MTX chemotherapy setting support the view of the dose-dependency of resveratrol in its health benefits.…”

Section: Discussionsupporting

confidence: 93%

Effects of Resveratrol Supplementation on Methotrexate Chemotherapy‐Induced Bone Loss

et al. 2017

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Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments. This study investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology. Young rats received five daily MTX injections at 0.75 mg/kg/day. RES was orally gavaged daily for seven days prior to, and during, five-day MTX administration. MTX reduced growth plate thickness, primary spongiosa height, trabecular bone volume, increased marrow adipocyte density, and increased mRNA expression of the osteogenic, adipogenic, and osteoclastogenic factors in the tibial bone. RES at 10 mg/kg was found not to affect bone health in normal rats, but to aggravate the bone damage in MTX-treated rats. However, RES supplementation at 1 mg/kg preserved the growth plate, primary spongiosa, bone volume, and lowered the adipocyte density. It maintained expression of genes involved in osteogenesis and decreased expression of adipogenic and osteoclastogenic factors. RES suppressed osteoclast formation ex vivo of bone marrow cells from the treated rats. These data suggest that MTX can enhance osteoclast and adipocyte formation and cause bone loss, and that RES supplementation at 1 mg/kg may potentially prevent these bone defects.

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Section: Discussionsupporting

confidence: 93%

Effects of Resveratrol Supplementation on Methotrexate Chemotherapy‐Induced Bone Loss

et al. 2017

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“…The differential concentration effects could be related to a possible drug interaction (between resveratrol and MTX) on bone tissue. Consistent with this, a recent study showed a synergistic effect of resveratrol and radiation treatment in killing radiation‐resistant prostate cancer cells and in treating prostate cancer cell xenograft tumors in mice . Furthermore, the observation of a harmful effect of resveratrol at 10 mg/kg (yet a protective effect at 1 mg/kg) on bone of MTX‐treated rats supports the proposed dose dependency of resveratrol health benefits .…”

Section: Potential Strategies For Preventing Methotrexate‐induced Bonsupporting

confidence: 68%

Childhood cancer chemotherapy–induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals

Chen

Hassanshahi

et al. 2017

Annals of the New York Academy of Sciences

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Intensive cancer chemotherapy causes significant bone loss, for which the mechanisms remain unclear and effective treatments are lacking. This is a significant issue particularly for childhood cancers, as the most common ones have a >75% cure rate following chemotherapy; there is an increasing population of survivors who live with chronic bone defects. Studies suggest that these defects are the result of reduced bone from increased marrow fat formation and increased bone resorption following chemotherapy. These changes probably result from altered expression/activation of regulatory molecules or pathways regulating skeletal cell formation and activity. Treatment with methotrexate, an antimetabolite commonly used in childhood oncology, has been shown to increase levels of proinflammatory/pro-osteoclastogenic cytokines (e.g., enhanced NF-κB activation), leading to increased osteoclast formation and bone resorption, as well as to attenuate Wnt signaling, leading to both decreased bone and increased marrow fat formation. In recent years, understanding the mechanisms of action and potential health benefits of selected nutraceuticals, including resveratrol, genistein, icariin, and inflammatory fatty acids, has led to preclinical studies that, in some cases, indicate efficacy in reducing chemotherapy-induced bone defects. We summarize the supporting evidence.

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“…The number of surviving colonies were counted for evaluation of cell viability. Dose-survival curves for each experiment were constructed by plotting the mean SFs semi-logarithmically as a function of IR dose ( Chen et al, 2017 ). The data were analyzed and survival curves were plotted following the linear quadratic (LQ) model using GraphPad Prism 6.0 software (GraphPad Software, United States).…”

Section: Methodsmentioning

confidence: 99%

Simvastatin Sensitizes Radioresistant Prostate Cancer Cells by Compromising DNA Double-Strand Break Repair

et al. 2018

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Prostate cancer (PCa) is one of the most prevalent male cancers in western world. Radiation therapy (RT) is commonly used to treat PCa patients. However, a certain proportion of patients develop radioresistant PCa cells, which results in metastatic disease. Statins, which inhibit 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, are commonly used to treat hypercholesterolemia, exhibiting beneficial effects on cardiovascular diseases and on several types of cancers, including PCa. However, the mechanistic details and crosstalk between statins and RT in PCa cells remain unknown. In this study, radioresistant DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells were used to evaluate whether simvastatin could enhance the effect of ionizing radiation (IR). The crucial molecules that associated with simvastatin elevated radiosensitivity in PCa cells were explored. Our results demonstrated that a combination treatment with simvastatin and IR synergistically induced apoptosis of radioresistant PCa cells. In addition, simvastatin appeared to compromise DNA double-strand breaks repair by activating the expressions of histone 2A family member X (γ-H2AX) and phospho-checkpoint kinase 1 (p-CHK1), suggesting an underlying mechanism for this radiosensitization of PCa cells. These findings reveal that simvastatin may be a potent therapeutic agent for co-treatment with radiation to overcome radioresistance in PCa cells.

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Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

Cited by 38 publications

References 52 publications

Effects of Resveratrol Supplementation on Methotrexate Chemotherapy‐Induced Bone Loss

Effects of Resveratrol Supplementation on Methotrexate Chemotherapy‐Induced Bone Loss

Childhood cancer chemotherapy–induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals

Simvastatin Sensitizes Radioresistant Prostate Cancer Cells by Compromising DNA Double-Strand Break Repair

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