Imperatorin Attenuates the Proliferation of MCF-7 Cells in Combination with Radiotherapy or Hyperthermia.

BACKGROUND: Breast cancer is one of the most common types of malignancies in the world. Cancer resistance is an unavoidable consequence of therapy with radiation or other modalities. Ongoing research aims to improve cancer response to therapy. AIM: The aim of this study was to evaluate the possible sensitization effect of imperatorin (IMP) in combination with external radiotherapy (ERT) or HT. METHODS: After treatment of MCF-7 breast cancer cells with IMP, cells were exposed to 4 Gy X-rays or HT (42 °C for 1 hour). The viability of MCF-7 cells was measured using an MTT assay. Furthermore, the expression of pro-apoptotic genes, including Bax, Bcl-2, caspase-3, caspase-8, and caspase- 9, was investigated using real-time PCR. The sensitizing effect of IMP in combination with ERT or HT was calculated and compared to ERT or HT alone. RESULTS: Results showed an increase in the expression of pro-apoptotic genes and downregulation of anti-apoptotic Bcl-2 following ERT and HT. Furthermore, cell viability was reduced following these treatments. IMP was able to augment these effects of ERT and HT. CONCLUSION: IMP could increase the efficiency of HT and ERT. This effect of IMP may suggest it as an adjuvant for increasing the therapeutic efficiency of ERT.

Modulation of Radiation-Induced NADPH Oxidases in Rat's Heart Tissues by Melatonin.

BACKGROUND: Experimental studies have shown that infiltration of inflammatory cells as well as upregulation of some cytokines play a central role in the development of late effects of ionizing radiation in heart tissues. Evidences have shown that an increased level of TGF-ß has a direct correlation with late effects of exposure to ionizing radiation such as chronic oxidative stress and fibrosis. Recent studies have shown that TGF-ß, through upregulation of pro-oxidant enzymes such as NOX2 and NOX4, promotes continuous ROS production and accumulation of fibrosis. OBJECTIVE: In present study, we aimed to evaluate the expression of NOX2 and NOX4 signaling pathways as well as possible modulatory effects of melatonin on the expression of these genes. MATERIAL AND METHODS: In this experimental study, four groups of 20 rats (5 in each) were used as follows; G1: control; G2: melatonin; G3: radiation; G4: radiation + melatonin. 100 mg/kg of melatonin was administrated before irradiation of heart tissues with 15 Gy gamma rays. 10 weeks after irradiation, heart tissues were collected for real-time Polymerase chain reaction (PCR). RESULTS: Results showed a significant increase in the expression of TGF-ß, Smad2, NF-kB, NOX2 and NOX4. The upregulation of NOX2 was more obvious by 20-fold compared to other genes. Except for TGF-ß, melatonin could attenuate the expression of other genes. CONCLUSION: This study indicated that exposure of rat's heart tissues to radiation leads to upregulation of TGF-ß-NOX4 and TGF-ß-NOX2 pathways. Melatonin, through modulation of these genes, may be able to alleviate radiation-induced chronic oxidative stress and subsequent consequences.

Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: a mechanistic review.

Glioblastoma, WHO grade IV astrocytoma, is the most aggressive type of brain tumors. These cancerous cells have a rapid growth rate, tendency to penetrate vital brain structures, molecular heterogeneity, etc. and this cancer is associated with a poor prognosis and low survival rate. Due to the resistance of glioblastoma cells to conventional therapeutic modalities (such as radiation therapy and chemotherapy) as well as the adverse effects of these modalities, the researchers have attempted to discover an appropriate alternative or adjuvant treatment for glioblastoma. Resveratrol, as an herbal and natural polyphenolic compound, has anti-tumoral property and has shown to be effective in GBM treatment. Resveratrol exerts its anti-tumoral effect through various mechanisms such as regulation of cell cycle progression and cell proliferation, autophagy, oxidant system, apoptosis pathways, and so on. Resveratrol in combination with radiation therapy and chemotherapy has also been used. In the present study, we summarized the current findings on therapeutic potentials of resveratrol in glioblastoma radiotherapy and chemotherapy.

The role of melatonin on radiation-induced pneumonitis and lung fibrosis: A systematic review.

PURPOSE: Pneumonitis and lung fibrosis, as the most common compliances of lung irradiation, can affect the quality of life. The use of radio-protective agents can ameliorate these injuries. This study aimed to review the potential protective role of melatonin in the treatment of radiation-induced Pneumonitis and lung fibrosis. METHODS: The current systematic study was conducted based on PRISMA guidelines to identify relevant literature on " the effect of melatonin on radiation-induced pneumonitis and lung fibrosis" in the electronic databases of Web of Science, Embase, PubMed, and Scopus up to January 2021. Eighty-one articles were screened in accordance with the inclusion and exclusion criteria of the study. Finally, eight articles were included in this systematic review. RESULTS: The finding showed that the lung irradiation-induced pneumonitis and lung fibrosis. The co-treatment with melatonin could alleviate these compliances through its anti-oxidant and anti-inflammatory actions. Melatonin through upregulation of some enzymes such as catalase, superoxide dismutase, glutathione, NADPH oxidases 2 and 4, dual oxidases 1 and 2, and also downregulation of malondialdehyde reduced oxidative stress following lung radiation. Moreover, melatonin through its anti-inflammatory effects, can attenuate the increased levels of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, SMAD2, interleukin (IL)-4, IL-4 receptor-a1 (IL4ra1), and IL-1 beta following lung radiation. The histological damages induced by ionizing radiation were also alleviated by co-treatment with melatonin. CONCLUSION: According to the obtained results, it was found that melatonin can have anti-pneumonitis and anti-fibrotic following lung irradiation.

Suberosin Attenuates the Proliferation of MCF-7 Breast Cancer Cells in Combination with Radiotherapy or Hyperthermia.

AIM: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin. BACKGROUND: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin- derived natural agent that has shown anti-inflammatory properties. OBJECTIVE: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated. METHODS: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of pro-apoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR. RESULTS: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability. CONCLUSION: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

Resveratrol Induces Apoptosis and Attenuates Proliferation of MCF-7 Cells in Combination with Radiation and Hyperthermia.

AIM: In the current in vitro study, we tried to examine the possible role of resveratrol as a sensitizer in combination with radiotherapy or hyperthermia. BACKGROUND: Breast cancer is the most common malignancy for women and one of the most common worldwide. It has been suggested that using non-invasive radiotherapy alone cannot eliminate cancer cells. Hyperthermia, which is an adjuvant modality, induces cancer cell death mainly through apoptosis and necrosis. However, cancer cells can also develop resistance to this modality. OBJECTIVE: The objective of this study was to determine possible potentiation of apoptosis when MCF-7 cells treated with resveratrol before hyperthermia or radiotherapy. METHODS: MCF-7 cancer cells were treated with different doses of resveratrol to achieve IC50%. Afterwards, cells treated with the achieved concentration of resveratrol were exposed to radiation or hyperthermia. Proliferation, apoptosis and the expression of pro-apoptotic genes were evaluated using flow cytometry, MTT assay and real-time PCR. Results for each combination therapy were compared to radiotherapy or hyperthermia without resveratrol. RESULTS: Both irradiation or hyperthermia could reduce the viability of MCF-7 cells. Furthermore, the regulation of Bax and caspase genes increased, while Bcl-2 gene expression reduced. Resveratrol potentiated the effects of radiation and hyperthermia on MCF-7 cells. CONCLUSION: Results of this study suggest that resveratrol is able to induce the regulation of pro-apoptotic genes and attenuate the viability of MCF-7 cells. This may indicate the sensitizing effect of resveratrol in combination with both radiotherapy and hyperthermia.