Molecular basis of ‘hypoxic’ breast cancer cell radio-sensitization: phytochemicals converge on radiation induced Rel signaling

Aravindan, Sheeja; Natarajan, Mohan; Herman, Terence S.; Awasthi, Vibhudutta; Aravindan, Natarajan

doi:10.1186/1748-717x-8-46

Cited by 27 publications

(18 citation statements)

References 65 publications

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“…Similarly, further evaluation of the role of NF-kB is needed in RSV+XRT in different cancers. In human breast cancer cells (MCF-7) (Aravindan et al, 2013), the inhibition of NF-kB-DNA binding activity by RSV+IR combined treatment, have been shown to trigger a cascade of events leading to suppression of 53 NF-kB signal transduction genes, which ultimately lead to cell death. These significant events by the synergistic effect of RSV+IR plus the known role of radiation in modulation of NF-kB (Linard et al, 2004;Gao et al, 2011;Presser et al, 2013), which in turn regulate several inflammatory response, highlights the need for the comprehensive analysis of the role of NF-kB in different cancer with combine treatment of RSV+IR.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic Effect of Resveratrol and Radiotherapy in Control of Cancers

Kma

2013

Asian Pacific Journal of Cancer Prevention

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Cancers will continue to be a threat to health unless they can be controlled by combinations of treatment modalities. In this review, evaluate the role of resveratrol (RSV) as a radiosensitizing agent was evaluated and underlying mechanisms holistically explored in different cancer models focusing on therapeutic possibilities. The ability of RSV to modify the effect of radiation exposure in normal and cancer cells has indeed been shown quite convincingly, the combination of RSV and IR exhibiting synergistic effects on different cancer cells. This is relevant since controlled exposure to IR is one of the most frequently applied treatments in cancer patients. However, radiotherapy (XRT) treatment regimes are very often not effective in clinical practice as observed in patients with glioma, prostate cancer (PCa), melanoma, for example, largely due to tumour radioresistant properties. Sensitization of IR-induced apoptosis by natural products such as RSV is likely to be relevant in cancer control and treatment. However, all cancers do not respond to RSV+IR in a similar manner. Therefore, for those such as the radioresistant PCa or melanoma cells, the RSV+IR regime has to be very carefully chosen in order to achieve effective and desirable outcomes with minimum toxicity to normal cells. They are reports that the highest concentration of 100 mM RSV and highest dose of 5 Gy IR are sufficient to kill cells by induction of apoptosis, indicating that RSV is effective in radiosensitizing otherwise radioresistant cells. In general, it has been shown in different cancer cells that RSV+XRT effectively act by enhancing expression of anti-proliferative and pro-apoptotic molecules, and inhibiting pro-proliferative and anti-apoptotic molecules, leading to induction of apoptosis through various pathways, and cell death. If RSV+XRT can suppress the signature of cancer stemness, enhance the radiosensitivity by either targeting the mitochondrial functionality or modulating the tumour necrosis factor-mediated or Fas-FasL-mediated pathways of apoptosis in different cancers, particularly in vivo, its therapeutic use in the control of cancers holds promise in the near future.

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Section: Discussionmentioning

confidence: 99%

“…In another study on the radiosensitizing effect of RSV on breast cancer, estrogen receptor positive human adenocarcinoma (MCF-7) breast cancer (BCa) cells were used (Aravindan et al, 2013). The cells, plated in 100 mm tissue culture plates containing 6 ml of complete growth medium, were allowed to grow up to 70-80% confluence.…”

Section: Breast Cancermentioning

confidence: 99%

Synergistic Effect of Resveratrol and Radiotherapy in Control of Cancers

Kma

2013

Asian Pacific Journal of Cancer Prevention

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“…NF-κB was activated by irradiation and plays a key role in radio-adaptive resistance under ionizing radiation in prostate and breast cancer (31)(32)(33). However, the activation of NF-κB could reduce the therapeutic efficacy of radiotherapy in cancer cells (34) and blocking NF-κB activation increased the apoptosis response (35,36).…”

Section: Discussionmentioning

confidence: 99%

MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo

et al. 2015

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Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal‑H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti‑growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-κB expression and IκBα phosphorylation was attenuated in MG132 plus irradiation-treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo.

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“…The pleiotropic nature of the effects of these agents on apoptosis and arrest of cell growth has been emphasized, and their potential use in association with chemotherapy drugs has been acknowledged. Novel strategies based on a strategic combination of phytochemicals with broad-spectrum action together with radiation or chemotherapy agents aimed at overcoming resistance to apoptosis and enhancing sensitivity to treatment are also currently being considered [59,60]. …”

Section: Methodsmentioning

confidence: 99%

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Block

Gyllenhaal

Lowe

et al. 2015

Seminars in Cancer Biology

238

191

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Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a substantial and longstanding problem, so a proposed agenda for future research is offered.

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Molecular basis of ‘hypoxic’ breast cancer cell radio-sensitization: phytochemicals converge on radiation induced Rel signaling

Cited by 27 publications

References 65 publications

Synergistic Effect of Resveratrol and Radiotherapy in Control of Cancers

Synergistic Effect of Resveratrol and Radiotherapy in Control of Cancers

MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo

Designing a broad-spectrum integrative approach for cancer prevention and treatment

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