Radiation-induced Apoptosis Research Articles

CGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells.

Cyclic GMP-AMP synthase (cGAS) plays an important role in biological responses to pathogens. The activation of the cGAS pathway in immune cells is known to induce antitumor effects, but the role of cGAS in cancer cells remains poorly understood. In silico analysis using public databases suggested that high cGAS expression in head and neck squamous cell carcinoma (HNSCC) is indicative of a poor prognosis for HNSCC patients. We therefore investigated the role of cGAS in malignancies and the cellular radiation response of human HNSCC cells (SAS and Ca9-22) in vitro, because radiotherapy is one of the treatments most commonly used for HNSCC. Although cGAS knockdown failed to suppress the proliferation of non-irradiated HNSCC cells, it enhanced the radiosensitivity of HNSCC cells. The administration of the cGAS agonist increased the radioresistance of HNSCC cells. cGAS knockdown increased radiation-induced mitotic catastrophe, apoptosis, or cellular senescence, depending on the cell line, and this cell line-dependent response might be due to different responses of p21 after irradiation. Collectively, our findings indicate that the cGAS pathway regulates the radioresistance of HNSCC cells.

Improving Patients' Life Quality after Radiotherapy Treatment by Predicting Late Toxicities.

Simple SummaryOver 50% of patients with cancer will receive radiotherapy treatment. Five to ten percent of patients who received radiotherapy will develop side effects. Identifying these patients before treatment start would allow for treatment modification to minimize these effects and improve the life quality of these patients. Our team developed a test, which allows predicting these secondary effects before starting the treatment. This will help in proposing personalized treatments to improve the outcome. This review presents how this test is performed, its results, as well as its modification in order to be used in hospitals.Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decision making in precision radiation oncology. This literature review summarizes the development and bases of this assay, as well as its clinical results and compares its results to the other available assays.

The Roles of Non-Coding RNAs in Radiotherapy of Gastrointestinal Carcinoma.

Radiotherapy (RT), or radiation therapy, has been widely used in clinical practice for the treatment of local advanced gastrointestinal carcinoma. RT causes DNA double-strand breaks leading to cell cytotoxicity and indirectly damages tumor cells by activating downstream genes. Non-coding RNA (including microRNAs, long non-coding RNAs (ncRNAs), and circular RNAs) is a type of RNA that does not encode a protein. As the field of ncRNAs increasingly expands, new complex roles have gradually emerged for ncRNAs in RT. It has been shown that ncRNAs can act as radiosensitivity regulators in gastrointestinal carcinoma by affecting DNA damage repair, cell cycle arrest, irradiation-induced apoptosis, cell autophagy, stemness, EMT, and cell pyroptosis. Here, we review the complex roles of ncRNAs in RT and gastrointestinal carcinoma. We also discuss the potential clinical significance and predictive value of ncRNAs in response to RT for guiding the individualized treatment of patients. This review can serve as a guide for the application of ncRNAs as radiosensitivity enhancers, radioresistance inducers, and predictors of response in RT of gastrointestinal carcinoma.

Enhanced radiosensitivity by 6-thio-dG via increasing telomere dysfunction and ataxia telangiectasia mutated inhibition in non-small cell lung cancer

ObjectiveTo investigate the radiosensitivity of 6-thio-dG and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). MethodsH1299 and A549 NSCLC cells were pretreated with 6-thio-dG for one week and then exposed to γ-irradiation. Cell proliferation and survival were quantified using clonogenic assays. DNA damage was assessed using immunofluorescence for γH2AX. Telomere dysfunction-induced foci analysis was performed by the co-localization of telomere signals (FISH) and γH2AX. Telomere fusion was defined as two telomere signals merged into one at the chromosome by immuno-FISH in metaphase spreads. Proteins related to the DNA damage response were detected using Western blot analysis. Apoptosis wasanalyzed using flow cytometry and Western blot. ResultsThe presence of 6-thio-dG increased the radio sensitivity of H1299 and A549 ​cells (P<0.05), but had no effect on the normal human lung fibroblast line, MRC5. 6-thio-dG pretreatment significantly reduced the clonogenic potential induced by γ-ray irradiation and aggravated genomic DNA and telomeric DNA damage (P<0.05). In addition, 6-thio-dG pretreatment effectively increased γ-ray irradiation induced telomere dysfunction (P<0.05), resulting in disruption of chromosome stability and inhibition of the ATM pathway, thereby impairing genomic DNA and telomeric DNA repair, which was closely associated with enhanced drug-mediated radiation-induced apoptosis. Conclusions6-thio-dG increases the radiosensitivity of NSCLC by inhibiting ATM and inducing telomere dysfunction, which can potentially be used as a strategy for radiotherapy for NSCLC.

MiR-513a-3p promotes radiation-induced apoptosis of human lung cells by inhibiting glutathione S-transferase P1.

Radiotherapy is a common treatment for lung cancer. However, radiation pneumonitis caused by radiotherapy can affect the quality of life and prognosis of lung cancer patients. miR-513a-3p has been found to sensitize human lung adenocarcinoma cells to chemotherapy by targeting glutathione S-transferase P1 (GSTP1). Here, we found that x-ray induced the apoptosis of BEAS-2B and miR-513a-3p expression in a dose- and time-dependent manner, and miR-513a-3p-mimic significantly increased x-ray induced apoptosis, while miR-513a-3p-inhibitor significantly decreased x-ray induced apoptosis. Dual luciferase gene reporter system showed that miR-513a-3p targeted to inhibit the expression of GSTP1 in BEAS-2B cells. Moreover, knockdown of GSTP1 significantly increased, while overexpression of GSTP1 decreased the apoptosis of BEAS-2B induced by x-ray. Importantly, overexpression of GSTP1 significantly reduced miR-513a-3p-mimic elevated x-ray -induced apoptosis in BEAS-2B cells. In conclusion, x-ray caused increased expression of miR-513a-3p, and miR-513a-3p promoted x-ray-induced apoptosis of human lung cells by inhibiting GSTP1.

In vitro radiosensitization by eribulin in human cancer cell lines.

BackgroundThe objective was to to determine the radiosensitizing properties of eribulin and the potential mechanisms of radiosensitization in cervical (HeLa) and pharyngeal (FaDu) cancer cell lines.Materials and methodsCytotoxicity was evaluated by the crystal violet method. The 10% and 50% inhibitory concentration (IC10, IC50) for 24-hour drug exposure were determined. The surviving fraction at 2 Gy (SF2) and the sensitizer enhancement ratio (SER) were calculated from radiation cell survival curves in the presence or absence of eribulin. Combination index (CI) was calculated to determine if there is a true synergistic interaction between eribulin and irradiation. Cell cycle changes were assessed by propidium iodide staining and flow cytometry. Apoptotic cells were detected by annexin V and TUNEL-assay.ResultsMean IC50s and IC10s were 1.58 nM and 0.7 nM and 0.7 nM and 0.27 nM for HeLa and FaDu cells, respectively. Radiosensitization was observed in both lines with a SER up to 2.71 and 2.32 for HeLa and FaDu cells, respectively. A true synergistic effect was showed with a CI of 0.82 and 0.76 for HeLa and FaDu cells, respectively. Eribulin induced significant G2/M cell arrest and marked apoptosis. Irradiation combined with 3 nM eribulin increased the apoptotic response to radiation in Hela cells.ConclusionEribulin shows a true in vitro radiosensitizing effect in HeLa and FaDu cells by inducing significant G2/M phase arrest. In HeLa, the enhancement radiation-induced apoptosis could be an additional mechanism of radiosensitization. Further studies are needed to evaluate the clinical benefits of concurrent eribulin and radiotherapy as a novel therapeutic strategy for cancer.

Enhanced autophagy promotes radiosensitivity by mediating Sirt1 downregulation in RM-1 prostate cancer cells

Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC.

Knockdown of Annexin A2 Enhances Radiosensitivity by Increasing G2/M-Phase Arrest, Apoptosis and Activating the p38 MAPK-HSP27 Pathway in Nasopharyngeal Carcinoma.

Annexin A2 (ANXA2) has been found to be involved in cancer proliferation, metastasis and prognosis; however, its exact role in nasopharyngeal carcinoma (NPC) radioresistance remains unknown. We found that ANXA2 expression was correlated with prognosis in NPC patients, and longer overall survival in NPC patients with low ANXA2 expression than those with high ANXA2 expression. ANXA2 knockdown increased the radiosensitivity in radioresistant NPC cells, and ANXA2 overexpression decreased the radiosensitivity in NPC cells. Knocking-down ANXA2 expression increased the irradiation-induced apoptosis of radioresistant NPC cells, and ANXA2 overexpression decreased the irradiation-induced apoptosis of NPC cells. ANXA2 knockdown induced G2/M phase arrest in NPC cells post-irradiation, and ANXA2 overexpression abrogated G2/M phase arrest in NPC cells post-irradiation. ANXA2 overexpression resulted in inhibition of the p38 MAPK-HSP27 pathway, while ANXA2 knockdown resulted in activation of the p38 MAPK-HSP27 pathway. In addition, ANXA2 knockdown increased the radiosensitivity of the xenografted tumors in nude mice. Our data demonstrate that knockdown of Annexin A2 enhanced radiosensitivity in NPC by increasing G2/M-phase arrest, apoptosis and activating the p38 MAPK-HSP27 pathway. ANXA2 may be a promising target used to overcome radioresistance in NPC.

High-Sulfated Hyaluronic Acid Ameliorates Radiation-Induced Intestinal Damage Without Blood Anticoagulation

PurposeMany growth factors, such as fibroblast growth factors (FGFs), are useful for the treatment or prevention of radiation damage after radiation therapy. Although heparin can be supplemented to increase the therapeutic effects of FGFs, it possesses strong anticoagulant effects, which limit its potential for clinical use. Therefore, chemically sulfated hyaluronic acid (HA) was developed as a safe alternative to heparin. This study examined the involvement of sulfated HA in radioprotective and anticoagulant effects. Methods and MaterialsFGF1 was administered intraperitoneally to BALB/c mice with sulfated HA 24 hours before or after total body irradiation with γ-rays. Several radioprotective effects were examined in the jejunum. The blood coagulation time in the presence of sulfated HA was measured using murine whole blood. ResultsFGF1 with high-sulfated HA (HA-HS) exhibited almost the same level of in vitro mitogenic activity as heparin, whereas FGF1 with HA or low-sulfated HA exhibited almost no mitogenic activity. Furthermore, HA-HS had high binding capability with FGF1. FGF1 with HA-HS significantly promoted crypt survival to the same level as heparin after total body irradiation and reduced radiation-induced apoptosis in crypt cells. Moreover, pretreatment of HA-HS without FGF1 also increased crypt survival and reduced apoptosis. Crypt survival with FGF1 in the presence of HA depended on the extent of sulfation of HA. Moreover, the blood anticoagulant effects of sulfated HA were weaker than those of heparin. As sulfated HA did not promote the reactivity of antithrombin III to thrombin, it did not increase anticoagulative effects to the same extent as heparin. ConclusionsThis study suggested that HA-HS promotes the radioprotective effects of FGF1 without anticoagulant effects. HA-HS has great potential for practical use to promote tissue regeneration after radiation damage.

3D reconstructed brain images reveal the possibility of the ogg1 gene to suppress the irradiation-induced apoptosis in embryonic brain in medaka (Oryzias latipes)

The accumulation of oxidative DNA lesions in neurons is associated with neurodegenerative disorders and diseases. Ogg1 (8-oxoG DNA glycosylase-1) is a primary repair enzyme to excise 7,8-dihydro-8-oxoguanine (8-oxoG), the most frequent mutagenic base lesion produced by oxidative DNA damage. We have developed ogg1-deficient medaka by screening with a high resolution melting (HRM) assay in Targeting-Induced Local Lesions In Genomes (TILLING) library. In this study, we identified that ogg1-deficient embryos have smaller brains than wild-type during the period of embryogenesis and larvae under normal conditions. To reveal the function of ogg1 when brain injury occurs during embryogenesis, we examined the induction of apoptosis in brains after exposure to gamma-rays with 10 Gy (137Cs, 7.3 Gy/min.) at 24 h post-irradiation both in wild-type and ogg1-deficient embryos. By acridine orange (AO) assay, clustered apoptosis in irradiated ogg1-deficient embryonic brains were distributed in a similar manner to those of irradiated wild-type embryos. To evaluate possible differences of gamma-ray induced apoptosis in both types of embryonic brains, we constructed 3D images of the whole brain based on serial histological sections. This analysis identified that the clustered apoptotic volume was about 3 times higher in brain of irradiated ogg1-deficient embryos (n = 3) compared to wild-type embryos (n = 3) (P = 0.04), suggesting that irradiation-induced apoptosis in medaka embryonic brain can be suppressed in the presence of functional ogg1. Collectively, reconstruction of 3D images can be a powerful approach to reveal slight differences in apoptosis induction post-irradiation.

SND1 Promotes Radioresistance in Cervical Cancer Cells by Targeting the DNA Damage Response.

Background: Radiotherapy is one of the most effective therapeutic strategies for cervical cancer patients, although radioresistance-mediated residual and recurrent tumors are the main cause of treatment failure. However, the mechanism of tumor radioresistance is still elusive. DNA damage response pathways are key determinants of radioresistance. The purpose of this study was to investigate the role and mechanism of SND1 in radioresistance of cervical cancer. Methods: A stable HeLa cell line with SND1 knockout (HeLa-KO) was generated through a modified CRISPR/Cas9 double-nicking gene editing system. The stable CaSki cell lines with SND1 knockdown (CaSki-Ctrl, CaSki-SND1-sh-1, CaSki-SND1-sh-2) were constructed through lentivirus transfection with the pSil-SND1-sh-1 and pSil-SND1-sh-2 plasmids. Results: It was observed that SND1 deficiency significantly increased the radiosensitivity of cervical cancer cells. It was also found that silencing SND1 promotes radiation-induced apoptosis. Significantly, the cells with a loss of SND1 function exhibited inefficient ataxia telangiectasia mutated pathway activation, subsequently impairing DNA repair and G2/M checkpoint arrest. In addition, threonine 103 is an important phosphorylation site of SND1 under DNA damaging stress. Conclusion: Collectively, the results of this study reveal a potent radiosensitizing effect of silencing SND1 or T103 mutation on cervical cancer cells, providing novel insights into potential therapeutic strategies for cervical cancer treatment.

Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer

Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of Skp2 confers sensitivity to irradiation of CRC cells. Skp2 deficiency enhances irradiation-induced intrinsic apoptosis by facilitating E3 ligase FBW7-mediated Mcl-1 ubiquitination and degradation. Knockout of Skp2 sensitizes CRC cells to irradiation treatments in vivo. Our findings indicate that Skp2 stabilizes Mcl-1, and targeting Skp2 in combination with traditional radiotherapy might be efficacious in treating CRC.

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum.

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.

High density lipoprotein nanoparticle as delivery system for radio-sensitising miRNA: An investigation in 2D/3D head and neck cancer models

Radiotherapy is one of the main treatment options for head and neck cancer patients. However, its clinical efficacy is hindered by both radiation induced side effects and radio-resistance. Radio-sensitising approaches with acceptable toxicity are being actively investigated. Among these, RNA therapeutics have great potentials as radio-sensitisers owing to their ability to target pathways specific to radio-resistance. However, their clinical translation is challenging due to delivery issues. Herein, we report the application of high-density lipoprotein nanoparticle (HDL NPs) as a biocompatible delivery system for a well-established radio-sensitising RNA, miR-34a. A simple/fast microfluidic based technique was used to prepare miR-34a-HDL NPs. Profiling of the radiation response in the UM-SCC-1 head and neck cancer cell line confirmed reduced metabolic activity and increased radiation induced apoptosis upon treatment with miR-34a-HDL NPs. The radio-sensitising properties of miR-34a-HDL NPs were further confirmed in a more biologically relevant co-culture spheroid model of head and neck cancer. Increased apoptotic activity and disrupted cell cycle were induced by miR-34a delivered by HDL NPs. The enhanced radio-biologic effects observed in both 2D and 3D models confirmed the utility of HDL NPs as an efficient delivery system for radio-sensitising RNA.

Association of Radiation-induced CD4 and CD8 T-Lymphocyte Apoptosis with Radiation-induced Fibrosis after Breast Conserving Therapy

Background: Around 70% of early breast cancer patients choose breast conserving therapy (BCT), with equal overall and disease-free survival rates compared to mastectomy. As a result, treatment decisions are currently guided by cosmetic outcomes and quality of life (QoL). Unfortunately, 13.4% of all BCT patients are affected by a grade 2 of radiation-induced fibrosis (RIF) of the breast. The individual risk of RIF could be predicted based the reduced radiation-induced lymphocyte apoptosis (RILA).

Loco-regional radiosensitizing nanoparticles-in-gel augments head and neck cancer chemoradiotherapy

The therapeutic gain in loco-regionally advanced unresectable head and neck squamous cell carcinoma (HNSCC) is limited with the traditional use of concurrent chemoradiotherapy (CRT) owing to dose-limiting toxicities of systemic clinical radiosensitizers. Delivery through regional platforms is challenging due to limited drug permeation but allows spatio-temporal control of combinatorial regimens locally to overcome drug resistance. We address these challenges by developing biodegradable gellan- and lipid-based dual nanocarriers-in-ion-triggered porous mucoadhesive hydrogels for enhanced site-specific delivery of clinically relevant radiosensitizers i.e. cisplatin and paclitaxel. Interestingly, the nanoparticle-in-gel prolonged the tumor bioaccumulation of both the chemotherapeutic drugs with reduced systemic absorption, thereby improving in vivo efficacy which was confirmed by PET-CT imaging and safety as compared to systemic commercial formulations approved for HNSCC chemoradiotherapy. The nanoparticles facilitated intracellular radiosensitizer uptake and cell arrest to synergistically enhance radiation-induced DNA nicks and apoptosis. Our findings suggest the clinical potential of the present platform in the loco-regional management of HNSCC requiring curative CRT.

Environmental Enrichment Increases Radiation-induced Apoptosis Not Spontaneous Apoptosis in Mouse Intestinal Crypt Cells.

An enriched environment (EE) modifies apoptotic cell death and promotes cell proliferation in the central nervous system (CNS) in mice. However, few studies have examined the effects of an EE on apoptosis in non-CNS organs in model orgamisms. In addition, the intestinal tract is one of organs at high-risk of carcinogenesis after radiation exposure. Herein we evaluated the effects of an EE on spontaneous and radiation-induced apoptosis in intestinal crypt cells of mice. Juvenile (3-week-old) and adult (11-week-old) male B6C3F1 mice were housed in a standard environment or EE for 8 weeks and then were whole-body irradiated with 2 Gy X-rays. Apoptosis in the small intestine and colon was analyzed with antibody against cleaved caspase 3. The EE significantly reduced body weight; adipose tissue weight; and serum levels of total cholesterol, triglyceride, leptin, and insulin. Although EE did not change the spontaneous apoptotic index without irradiation, it significantly increased the index after irradiation in the colonic crypt. The apoptotic index in the small intestinal crypt showed similar patterns. An EE enhances radiation-induced apoptosis of stem/progenitor cells in the small intestine and colon without affecting spontaneous apoptosis. An EE may thus reduce the risk of cancer in the intestinal tract after radiation exposure such as radiotherapy.

Puerarin Reduces Radiation-Induced Vascular Endothelial Cell Damage Via miR-34a/Placental Growth Factor.

The aim is to explore the protective effects of Puerarin on radiation-induced vascular endothelial cell damage and its underlying mechanism. The apoptosis and DNA damage of Human umbilical vascular endothelial cells (HUVECs) exposed to radiation alone or in combination with glucose in the exposed group were significantly elevated (P < .05) compared with those in the control group. The Puerarin-treated HUVECs showed significant reduction in the radiation-induced apoptosis and DNA damage (P < .05). Furthermore, X-ray irradiation significantly increased the expression of miR-34a, which was reversed by pre-treatment with Puerarin. Placental Growth Factor (PLGF) was a target gene of miR-34a. The expression of PLGF in the peripheral blood of patients receiving radiotherapy significantly increased with an increase in the cumulative dose of radiation (P < .05), after which it began to decrease at the fourth week (P < .05) and then remained at a low level until the end of radiotherapy. Puerarin exerts a radioprotective effect by decreasing DNA damage and apoptosis through miR-34a-targeted PLGF.

Yiqi Jiedu herbal decoction attenuates the 2 Gy 60Co γ ray induced spleen injury by inhibiting apoptosis and modulating the immune balance

Ethnopharmacological RelevanceIrradiation-induced immunosuppression often occurs during radiotherapy in patients, which would increase the risk of opportunistic infections. Many Chinese herbal prescriptions or natural extracts have recently attracted increased radiation protection and therapy attention due to their low toxicity. Aim of the studyThe present study aimed to investigate the protective effects of Yiqi Jiedu (YQJD) decoction on spleen injury induced by 2 Gy 60Co γ ray in mice. Materials and methodsA total of 180 Balb/c mice were randomly divided into five groups: blank control (Ctrl), model (IR), positive drug (IRA), low-dose YQJD decoction (IRL), and high-dose YQJD decoction (IRH). After a ten-day intervention, mice were exposed to a single dose of total body irradiation (2 Gy) and sacrificed on the 1st, 3rd, and 7th day after irradiation. The indicators include general observations and body weight, changes in peripheral hemogram, index and histopathology examination of the spleen, distribution of lymphocyte subsets, cytokine levels, and apoptosis in the spleen. ResultsIn comparison to the Ctrl group, the body weight, spleen index, peripheral blood cell, and splenocyte quantities decreased significantly after exposure, accompanied by a notable increase of apoptosis in spleen cells. Moreover, ionizing radiation also broke the balance of CD4+/CD8+, Th1/Th2, and Th17/Treg, triggering immune imbalance and immunosuppression. The above injuries occurred on the 1st day after exposure, worsened on the 3rd, and were relieved on the 7th day. However, the pretreatment of YQJD decoction increased the spleen index, improved the spleen structure, and inhibited radiation-induced apoptosis after exposure. Additionally, YQJD decoction has shown its ability to promote immunological balance recovery following exposure by regulating CD4+/CD8+, Th1/Th2, and Th17/Treg ratios, which may minimize the risk of infection. In addition, the high-dose of YQJD decoction showed a better protective effect than the low-dose group. ConclusionThe protective effects of YQJD decoction on 2 Gy 60Coγray induced spleen injury were confirmed in this study. This mechanism may be related to inhibiting apoptosis and modulating immune balance. This exploration might provide new insights into the use of Chinese herbs on radioprotection of the immune system.

Apigenin Enhanced Radiation-Induced Apoptosis/Necrosis by Sensitization of LNCaP Prostate Cancer Cells to 6 MV Photon Beams.

Objective Whereas prostate cancer (PrCa) may be unresponsive or moderately responsive to radiation therapy (RT)- most common modality for treatment of PrCa- patients must receive a high dose of RT In order to achieve appropriate tumour control. However, this increase in radiation dose may lead to severe adverse effects in normal tissues. Sensitization of PrCa to radiation provides an alternate approach to improve the therapeutic efficacy of RT. This study aims to assess the radiosensitisation effect of apigenin (Api) on a prostate cancer cell line (LNCaP). Materials and Methods In this experimental study, LNCaP cells were treated with 0-80 µM Api to investigate its effect on LNCaP cell viability and determine its half-maximal inhibitory concentration (IC50). Next, the cells were divided into four groups: i. Control, ii. Cells treated with the IC50 concentration of Api, iii. Cells treated with 2 Gy ionizing radiation (IR), and cells co-treated with Api and IR. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time polymerase chain reaction (PCR), and an Annexin V-FITC/PI assay were performed to assess cell survival, Bax and Bcl-2 expressions, and presence of apoptosis and necrosis. Results Api inhibited cell survival in a dose-dependent, but not time-dependent manner. Cells treated with Api had increased amounts of early apoptosis, late apoptosis, and secondary necrosis compared to the control group. This group also had decreased Bcl-2 gene expression and up-regulated Bax gene expression. Co-treatment with Api and IR significantly inhibited cell survival, and increased early apoptosis, late apoptosis and secondary necrosis compared to the other groups. There was a significant decrease in Bcl-2 gene expression along with up-regulation of Bax gene expression, and Bax/Bcl-2 ratio changes that favoured apoptosis. ConclusionApi inhibited PrCa cell survival and induced apoptosis as a single agent. In addition, Api significantly sensitized the LNCaP cells to IR and enhanced radiation-induced apoptosis.