The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.
Artesunate/therapeutic use* ; Carboplatin/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/therapeutic use* ; Doxorubicin/therapeutic use* ; Humans ; Neoplasms/radiotherapy* ; Radiation-Sensitizing Agents/therapeutic use*

Radiotherapy, frequently used for treatment of solid tumors, carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants, have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer treatment.
Antineoplastic Agents/*therapeutic use ; Apoptosis/drug effects/radiation effects ; Chromones/therapeutic use ; Combined Modality Therapy ; Cytoprotection/drug effects/radiation effects ; Humans ; Neoplasms/pathology/*radiotherapy ; Phenylpropionates/therapeutic use ; Plants ; Radiation Tolerance/drug effects ; Radiation-Sensitizing Agents/*therapeutic use ; *Radiotherapy

Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Taxoids ; therapeutic use

BACKGROUND AND OBJECTIVESonodynamic therapy (SDT) is a promising new approach for cancer therapy. The purpose of this study is to detect the effects of SDT on the cell proliferation of human lung adenocarcinoma cell SPCA-1, using Chlorin e6 as a sonosensitizing agent activated by ultrasound.

METHODSSPCA-1 and normal peripheral mononuclear cell (PMNC) were treated with ultrasound or Chlorin e6 alone and combined. Cell proliferation was determined by MTT assay, and cell morphology was studied by inverted microscope after 6 h treated.

RESULTS1.0 MHz ultrasound (1.0 W/ cm(2)-2.0 W/cm2 x 60 s) and Chlorin e6 (0.4 mg/mL-3.2 mg/mL) inhibited the cell proliferation of both SPCA-1 and PMNC cells in a intensity- and a dose-dependent manner respectively. Compared with the ultrasound (1.0 W/cm2 x 60 s) or Chlorin e6 (0.05 mg/mL-0.2 mg/mL) alone, the inhibitory effect on the cell proliferation was remarkably increased by the combination of ultrasound and chlorin e6 in SPCA-1 cells (P < 0.05), but no same effect was observed in PMNC cells (P > 0.05). Compared with the ultrasound (1.0 W/cm2 x 60 s) or chlorin e6 (0.2 mg/mL) alone, the combination treatment of ultrasound with Chlorin e6 induced more necrotic cells in SPCA-1 cells (P < 0.05).

CONCLUSIONThere was a significant selectively inhibitory effect of sonodynamic effect with Chlorin e6 on the SPCA-1 cell growth. Chlorin e6 may be a promising sonosensitizing agent for the treatment of non-small cell lung cancer.

Adenocarcinoma ; drug therapy ; therapy ; Cell Line, Tumor ; Humans ; Lung Neoplasms ; drug therapy ; therapy ; Porphyrins ; chemistry ; therapeutic use ; Radiation-Sensitizing Agents ; chemistry ; therapeutic use ; Ultrasonic Therapy ; methods

OBJECTIVETo study the radiosensitizing effect of resveratrol on hypopharyngeal carcinoma cell line FADU in vitro.

METHODSHypopharyngeal carcinoma cell line FADU was cultured in in vitro DMEM. Its inhibition on cell proliferation was detected using cytotoxicity test (MTT assay). The cell survival curve was drawn using clone formation to obtain sensitive enhancement ratio (SER). Changes of the cell cycle and cell apoptosis were analyzed using flow cytometry (FCM).

RESULTSResults of MTT showed the inhibition of resveratrol on FADU cells increased along with its concentrations (P < 0.05). Results of clone formation indicated the surviving fraction at 2 Gy (SF2) was 0.717 ± 0.062 in the irradiation group, and 0.426 ± 0.035 in the resveratrol plus irradiation group (with SER ranged 1.684 ± 0.178) with statistical difference (P = 0.007). Results of FCM showed that after radiation of 4 Gy radiation, cells at G2/M phase arrest increased, but cells at G1 decreased. After radiation of resveratrol for 24 h, cells at G1 decreased, but cells at G2/M phase and S phase arrest increased. When 4 Gy radiation combined resveratrol was used, cells at G2/M phase arrest significantly increased, but cells at G1 significantly decreased. The apoptosis rate was 1.94% ± 1.65% in the control group, 4.56% ± 0.92% in the irradiation group, 2.03% ± 1.46% in the resveratrol group, and 23.11% ± 7.22% in the resveratrol plus irradiation group. There was statistical difference between the resveratrol plus irradiation group and the rest 3 groups (P < 0.05).

CONCLUSIONResveratrol could enhance the radiosensitivity of hypopharyngeal carcinoma FADU cells in vitro possibly by inducing cell apoptosis and causing changes in the cell cycle distribution.

Apoptosis ; Carcinoma, Squamous Cell ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Head and Neck Neoplasms ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; therapeutic use ; Stilbenes ; therapeutic use

OBJECTIVETo investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer.

METHODSC57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments.

RESULTSMI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05).

CONCLUSIONMI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.

Animals ; Biological Products ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Dose Fractionation ; Dose-Response Relationship, Radiation ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Streptococcus

OBJECTIVETo observe the Chinese herbal medicine Selaginella-induced radiosensitization of terminal nasopharyngeal carcinoma (NPC).

METHODSTotally 180 patients with NPC were divided equally into 3 groups with the same radiotherapeutic protocols. The patients in group A received radiotherapy alone, those in group B were given daily Selaginella (30 g) prepared into 50 ml decoction during the entire course of radiotherapy, and those in group C had Selaginella 30 g daily in the late course of radiotherapy.

RESULTSThe complete remission rate of nasopharyngeal primary lesions in groups B and C was significantly higher than that in group A, with also significantly higher complete remission rates of the cervical lymph nodes. The acute toxicity of the skin and mucous membrane was milder in the latter two groups, but the differences were not significant.

CONCLUSIONSelaginella may induce radiosensitization for terminal NPC and does not increase the acute toxicity of radiotherapy.

Adult ; Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Phytotherapy ; Radiation-Sensitizing Agents ; therapeutic use ; Selaginellaceae ; chemistry ; Treatment Outcome

Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.
Animals ; Antineoplastic Agents ; therapeutic use ; Drug Carriers ; Energy Metabolism ; Glucose ; analogs & derivatives ; chemistry ; metabolism ; therapeutic use ; Glycoconjugates ; chemistry ; therapeutic use ; Glycolysis ; Glycosides ; chemistry ; Humans ; Ifosfamide ; analogs & derivatives ; chemistry ; therapeutic use ; Neoplasms ; diagnosis ; drug therapy ; metabolism ; Nitroimidazoles ; chemistry ; Radiation-Sensitizing Agents ; chemistry

OBJECTIVETo evaluate the radiosensitivity and toxicity of sodium glycididazole and cisplatin in concurrent chemoradiotherapy for local advanced nasopharyngeal carcinoma (NPC).

METHODSSixty patients with local advanced NPC (T3-4N2-3M0) were randomly divided into chemoradiotherapy group (n=30) and chemoradiotherapy plus sodium glycididazole group (n=30). All the patients received radiotherapy with (60)Co or 6-8 MV linear accelerator and concurrent injection of cisplatin at a weekly dose of 20 mg/m square. In sodium glycididazole group, the patients received injections of sodium glycididazole at 800 mg/m square prior to the radiotherapy 3 times a week.

RESULTSAt the end of the therapy and 3 month after the radiotherapy, a response rate of 100% was achieved in both of the groups. But at the end of the therapy, the chemoradiotherapy plus sodium glycididazole group showed a significantly higher rate of complete tumor remission than the chemoradiotherapy group (93.3% vs 73.33%, chi(2)=4.32, P=0.038). The patients in the two groups showed similar tolerance of the therapy during the observation.

CONCLUSIONSodium glycididazole plus cisplatin can accelerate the tumor remission and improve the complete remission rate in patients with local advanced NPC without causing severe toxicity.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; drug therapy ; radiotherapy ; Cisplatin ; administration & dosage ; Cobalt Radioisotopes ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Male ; Metronidazole ; analogs & derivatives ; therapeutic use ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Radiation-Sensitizing Agents ; therapeutic use

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.
Animals ; Apoptosis/drug effects ; Carcinoma, Lewis Lung/metabolism/*radiotherapy ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/radiation effects ; Gene Expression ; Lung Neoplasms/metabolism/*radiotherapy ; Mice ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Radiation Tolerance ; *Radiation-Sensitizing Agents ; Research Support, Non-U.S. Gov't ; Sphingosine/*analogs & derivatives/pharmacology/*therapeutic use