Cancer is one of the most prevalent chronic diseases of the world. Certain edible mushroom species are rich in antioxidants, which perform a vital role in preventing this risk in manifesting itself. Initial screening was followed by qualitative phytochemical analysis; estimation of total phenolic content, DPPH radical scavenging activity, and the ferric-reducing ability of plasma (FRAP) of the ethanolic and the aqueous extracts of 3 edible medicinal mushroom species, namely, Auricularia polytricha, Macrolepiota procera, and Pleurotus ostreatus. Furthermore, based on promising results from studies of antioxidant activities, these extracts were carried forward to study cytotoxic, antiproliferative, and antiapoptotic effects on breast (MCF-7), colon (COLO-205), and kidney (ACHN) cancer cell lines. Among all the extracts, the aqueous extract of P. ostreatus and the ethanolic extract of M. procera showed the highest cytotoxic effect on all 3 cancer cell lines, especially COLO-205. The scientific data obtained so far show that the aqueous extracts of all 3 species of mushrooms have a remarkable irreversible antiproliferative effect on COLO-205 compared with other cancer cell lines. This decrease in cell viability, morphological changes, and apoptotic hallmarks observed upon treatment with the extracts validated the anticancerous property of these mushroom species.

Photodynamic therapy (PDT) is a method to treat cancers using photosensitizer and light. PDT has been tried for several tumors. However, the clinical applications are limited by the toxicity of photosensitizer and narrow effect. Sulforaphane (SFN) is a material of isothiocyanate group and known to have anticancer effect. We evaluated the cytotoxic effect of PDT combined with SFN on human head and neck cancer cells. We measured the cell viability, extent of apoptosis and necrosis, reactive oxygen species (ROS) generation and caspase activation. Cell viability was decreased significantly by combination treatment. Cellular apoptosis and necrosis were increased in combination treatment compared to SFN or PDT. ROS generation was also higher in combination treatment than single treatment. In combination treatment group, apoptosis and necrosis were decreased by administration of sodium azide (SA) which is scavenger of ROS. Increased caspase activation in combination treatment was also inhibited by SA. Combination of PDT and SFN led to enhanced cytotoxic effect on head and neck cancer cells. Combination treatment promoted the ROS generation, which induced cell death through activation of caspase pathway.

In recent years, increasing evidence has emerged demonstrating that high-dose ascorbate bears cytotoxic effects on cancer cells in vitro and in vivo, making ascorbate a pro-oxidative drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. This anticancer effect of ascorbate is hypoxia-inducible factor-1α- and O2-dependent. However, whether the intracellular mechanisms governing this effect are modulated by epigenetic phenomena remains unknown. We treated human melanoma cells with physiological (200 μM) or pharmacological (8 mM) ascorbate for 1 h to record the impact on DNA methyltransferase (DNMT)-activity, histone deacetylases (HDACs), and microRNA (miRNA) expression after 12 h. The results were analyzed with the MIRUMIR online tool that estimates the power of miRNA to serve as potential biomarkers to predict survival of cancer patients. FACS cell-cycle analyses showed that 8 mMascorbate shifted BLM melanoma cells toward the sub-G1 fraction starting at 12 h after an initial primary G2/M arrest, indicative for secondary apoptosis induction. In pharmacological doses, ascorbate inhibited the DNMT activity in nuclear extracts of MeWo and BLM melanoma cells, but did not inhibit human HDAC enzymes of classes I, II, and IV. The expression of 151 miRNAs was altered 12 h after ascorbate treatment of BLM cells in physiological or pharmacological doses. Pharmacological doses up-regulated 32 miRNAs (≥4-fold) mainly involved in tumor suppression and drug resistance in ourpreliminary miRNA screening array. The most prominently up-regulated miRNAs correlated with a significantly increased overall survival of breast cancer or nasopharyngeal carcinoma patients of the MIRUMIR database with high expression of the respective miRNA. Our results suggest a possible epigeneticsignature of pharmacological doses of ascorbate in human melanoma cells and support further pre-clinical and possibly even clinical evaluation of ascorbate for melanoma therapy.

Epidemiological studies report that regular physical activity can reduce the risk for prostate cancer, the most common solid-tumor cancer in US men. Regular exercise alters the serum IGF axis in vivo and reduces cell proliferation while increasing apoptosis in serum-stimulated LNCaP prostate cancer cells in vitro. The present study tests the hypothesis that these effects on tumor cell lines are mediated by enhancement of the function of the p53 gene known to arrest cell growth and induce apoptosis. When LNCaP cells were cultured in exercise serum and compared with control serum, cell growth was reduced by 27%, and there was a similar 33% decrease in proliferating cell nuclear antigen protein, a marker for cell cycling. Apoptosis was increased by 371% with the exercise serum, and there was a 100% increase in p53 protein (75.2 +/- 2.0 vs. 38.2 +/- 2.0 pg/microg protein). When serum was used to stimulate LN-56 cells, a cell line with nonfunctional p53 derived from LNCaP, no significant reduction in cell growth or increase in apoptosis with the exercise serum was observed. These results indicate that exercise training alters serum factors in vivo that increase cellular p53 protein content and is associated with reduced growth and induced apoptosis in LNCaP prostate cancer cells in vitro.

Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine., a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells.To investigate the effect ofon osteosarcoma cells and its mechanism.Osteosarcoma MG63 and U2-OS cells were treated with, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect ofon Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay.inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed thatsuppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover,blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated.Our results suggest thatbroadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.

Photodynamic therapy (PDT), as a clinical cancer therapy, is a mild therapy, which involves application of photosensitizers (PSs) which located in target cells and then be irradiated by corresponding wawelength. The activation of PSs generates radical oxygenspecies ( ROS) to exert a selective cytotoxic activity for the target cells. Aloeemodin (AE) has been found to be a anti-tumor agent in many studies, and it also demonstrated to be a photosensitizer in recent years. In order to study the mechanism of aloe-emodin as a photosensitizer. In the present study, we investigated the mechanisms of photo-cytotoxicity induced by aloe-emodin in breast cancer MCF-7 cells. Analysis of cell proliferation evidenced that there was a dramatically depression after photodynamic treatment with aseries of aloe-emodin concentration and light doses showed. We observed changes apoptosis and demonstrated that the mechanisms of apoptosis were involved of mitochondrial and endoplasmic reticulum death pathway. The capacity of adhesion, migration and invasion of breast cells were measured usingWST8 and transwell assay and demonstrated that AE-PDT significantly inhibited adhesion, migration and invasion of MCF-7cells. The expression of MMP2, MMP9, VEGF and Nrf2 demonstrated that the metastasis was related to oxidative stress. Analysis of changes in cytoskeleton components (F-actin) evidenced cytoskeleton disorganization after treatment with AE-PDT. Taken together, the present results indicated that PDT with aloe emodin effectively suppressed cancer development in MCF-7cells, suggesting the potential of AE as one new photosensitizer in PDT can provide a new modility for treating cancer.

Photodynamic therapy (PDT), as a clinical cancer therapy, is a mild therapy, which involves application of photosensitizers (PSs) which located in target cells and then be irradiated by corresponding wawelength. The activation of PSs generates radical oxygenspecies ( ROS) to exert a selective cytotoxic activity for the target cells. Aloeemodin (AE) has been found to be a anti-tumor agent in many studies, and it also demonstrated to be a photosensitizer in recent years. In order to study the mechanism of aloe-emodin as a photosensitizer. In the present study, we investigated the mechanisms of photo-cytotoxicity induced by aloe-emodin in breast cancer MCF-7 cells. Analysis of cell proliferation evidenced that there was a dramatically depression after photodynamic treatment with aseries of aloe-emodin concentration and light doses showed. We observed changes apoptosis and demonstrated that the mechanisms of apoptosis were involved of mitochondrial and endoplasmic reticulum death pathway. The capacity of adhesion, migration and invasion of breast cells were measured usingWST8 and transwell assay and demonstrated that AE-PDT significantly inhibited adhesion, migration and invasion of MCF-7cells. The expression of MMP2, MMP9, VEGF and Nrf2 demonstrated that the metastasis was related to oxidative stress. Analysis of changes in cytoskeleton components (F-actin) evidenced cytoskeleton disorganization after treatment with AE-PDT. Taken together, the present results indicated that PDT with aloe emodin effectively suppressed cancer development in MCF-7cells, suggesting the potential of AE as one new photosensitizer in PDT can provide a new modility for treating cancer.

Cumulative evidence from research studies has shown that the shiitake culinary-medicinal mushroom, Lentinus edodes, is an excellent source of natural antitumor agents and is capable of inhibiting cancer cell growth. However, the cell signaling pathway that leads tumor cells to apoptosis is not well understood because many chemical compounds may be acting. This study investigated the chemopreventive effects of an L. edodes aqueous extract on human HEp-2 epithelial larynx carcinoma cells and normal human MRC-5 lung fibroblasts by identifying proliferative and apoptotic pathways. The chemical characterization of the dry powder was assessed by high-performance liquid chromatography. Antiproliferative and proapoptotic effects induced by the extract were evaluated by assessing proliferative markers, cell sorting through flow cytometry, and expression levels of apoptotic proteins with Western blotting. The results suggest that inhibition of cell proliferation was more prominent in HEp-2 than in MRC-5 cells. Cell death analysis showed the appearance of cell populations in the sub-G1 phase, with late apoptotic signal increased in a dose-dependent manner. In addition, the aqueous extract induced depolarization of mitochondria, activating the generation of intracellular reactive oxygen species in HEp-2 cells. These observations suggest that L. edodes extract may exert a chemopreventive effect, regulating mitotic induction of apoptogenic signals. These findings highlight the mushroom's pharmacological potential in cancer treatment.

Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.

Over many centuries, herbal remedies have treated a variety of ailments. This empiric observational approach has produced a number of leads for formulated medicines. Ganoderma lucidum extract was screened for its anti-proliferative activity using a panel of 26 human cancer cell lines. The six most sensitive hematologic cell lines were: HL-60 (ED50 26 microg/ml), U937 (63 microg/ml), K562 (50 microg/ml), Blin-1 (38 microg/ml), Nalm-6 (30 microg/ml) and RPMI8226 (40 microg/ml). Cell cycle analyses revealed a G2/M arrest, most prominently in HL-60 cells. Four hematopoietic cell lines (HL-60, Blin-1, U937, RPMI8226) were examined for apoptosis, which ranged between 21 and 92%. After exposure to G. lucidum extract, HL-60 cells became multinucleated with an increased DNA content. These results indicate that G. lucidum extract has a profound activity against leukemia, lymphoma and multiple myeloma cells and may be a novel adjunctive therapy for the treatment of hematologic malignancies.

AIM OF THE STUDY: The final goal of this work was to study the toxic and apoptosis effects induced by fractions from Ganoderma lucidum [Ganoderma lucidum (Curtis) P. Karst.; Ganodermataceae Donk] on NB4 human leukemia cells. MATERIALS AND METHODS: Two aqueous extracts and a methanol-extracted column-chromatography semipurified fraction were obtained from Ganoderma lucidum fruiting body. Flow cytometry analyses were used to measure cell viability, cell cycle and DNA fragmentation and to quantify apoptosis. Western-blot analyses were used to quantify changes in apoptosis proteins and intracellular kinases. RESULTS: Aqueous extracts slightly reduce cell viability and induce DNA fragmentation in NB4 cells. Methanol-extracted semipurified fraction at dilutions down to 15% or 40% of the initial fraction concentration reduced significantly the viability of these leukemia cells (treated for 19h) with induction of DNA fragmentation and induction of apoptosis. Overmore, the dilution down to 15% of the initial E3 concentration induced a reduction of p53 levels, of the Bcl2/Bax relationship as well as reduced levels of both unphosphorylated and phosphorylated Akt (Protein kinase Akt, protein kinase B) and Erk (Erk1 and 2). CONCLUSIONS: Induction of apoptosis and alterations in signal transduction kinases (Akt and Erk) are produced by active fractions from Ganoderma lucidum on human leukemia cells. These data could be of important relevance from the viewpoint of antitumor actions of compounds from Ganoderma lucidum. Eventual therapy applications in leukemia cells might be developed.

Ganoderma lucidum (Reishi), an oriental medical mushroom, has been widely used in Asian countries for centuries to prevent or treat different diseases, including cancer. However, the mechanism(s) responsible for the effects of Ganoderma lucidum on cancer cells remain to be elucidated. We have previously demonstrated that Ganoderma lucidum down-regulated the expression of NF-kappaB-regulated urokinase plasminogen activator (uPA) and uPA receptor (uPAR), which resulted in suppression of cell migration of highly invasive human breast and prostate cancer cells. In this study, we investigated the effects of Ganoderma lucidum on cell proliferation, cell cycle, and apoptosis in human prostate cancer cells PC-3. Our data demonstrate that Ganoderma lucidum inhibits cell proliferation in a dose- and time-dependent manner by the down-regulation of expression of cyclin B and Cdc2 and by the up-regulation of p21 expression. The inhibition of cell growth was also demonstrated by cell cycle arrest at G2/M phase. Furthermore, Ganoderma lucidum induced apoptosis of PC-3 cells with a slight decrease in the expression of NF-kappaB-regulated Bcl-2 and Bcl-xl. However, the expression of proapoptotic Bax protein was markedly up-regulated, resulting in the enhancement of the ratio of Bax/Bcl-2 and Bax/Bcl-xl. Thus, Ganoderma lucidum exerts its effect on cancer cells by multiple mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

BACKGROUND/AIMS:We aimed to explore whether ganoderma lucidum polysaccharide (GLP) exhibits antitumor effect on cervical cancer cells.

METHODS AND RESULTS:Different concentration of GLP was used to treat cervical cell. The data from cell counting kit-8 assay proved that the optimal working concentration and time of GLP were 200µg/mL and treated for 48 h. The transwell assay demonstrated that GLP could attenuate the invasion and migration abilities of cervical cancer cells. Moreover, flow cytometry illustrated that GLP could promote the apoptosis of cervical cancer cells and limit the cycle of cervical cancer cells. Western blot assay discovered that the expression of proapoptosis proteins including Bax, Cleaved Caspases 3 and 9 increased and the antiapoptosis protein Bcl-2 decreased after treated with GLP. Moreover, we found that the expression of E-cadherin was increased, and N-cadherin, Vimentin, and Slug were decreased. Meanwhile, the expression of phosphorylated-JAK and phosphorylated-STAT5 was also decreased in cervical cancer cells treated by GLP, suggesting the inhibitory effect on JAK/STAT5 pathways.

CONCLUSIONS:All of these data illustrated that GLP could alleviate the activity and aggressiveness, block the cell cycle, and promote the apoptosis of cervical cancer cells, which were possible via inhibiting epithelial-mesenchymal and JAK/STAT5 pathways.

GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of Grifola frondosa with novel sugar compositions and protein sequencing. The present study aims to investigate its effects on the cell cycle, differential proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle at S phase. GFG-3a treatment resulted in the differential expression of 21 proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM, HSP90AB1, and GRP78 involved in apoptosis and stress response. qRT-PCR and Western blot analysis also suggested that GFG-3a could increase the expressions of Caspase-8/-3, p53, Bax, and Bad while decrease the expressions of Bcl2, Bcl-xl, PI3K, and Akt1. These results indicated that the stress response, p53-dependent mitochondrial-mediated, Caspase-8/-3-dependent, and PI3k/Akt pathways were involved in the GFG-3a-induced apoptosis process in SGC-7901 cells. These findings might provide a basis to prevent or treat human gastric cancer with GFG-3a and understand the tumor-inhibitory molecular mechanisms of mushroom glycoproteins.

It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that HE acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma.

Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

This study evaluated the effects and mechanism of action of combining irreversible electroporation (IRE) and photodynamic therapy (PDT) in breast cancer cellsand. Jin's formula was used to assess killing efficacy of different IRE+PDT dosing combinations in breast cancer MCF-7 cells. Flow cytometry, high-content imaging, and confocal laser scanning microscopy were used to detect apoptosis. qRT-PCR and western blotting were used to evaluate expression of apoptosis-related genes and proteins. IRE+PDT combination therapy was administered to BALB/C mice with breast cancer tumors in vivo; tumor size was used to assess treatment efficacy. Killing mechanisms were examined using transmission electron microscopy and immunohistochemistry. We found that IRE+PDT combination therapy produced significant synergistic killing effects in breast cancer cells (highest Jin q value of 1.32). Early apoptosis rates were significantly higher in the IRE+PDT group (16.0%) than in IRE-alone (7.6%) and PDT-alone (4.6%) groups (<0.05). qRT-PCR showed higher Caspase-1, -3, -5, -6, -7, -8, and -9 and TNFRSF1A expression with IRE+PDT than with control. Western blots showed increased cleaved Caspase-3, -7, and -9, and PARP levels in the IRE+PDT group.tumor suppression rate for IRE (1200 V)+PDT (10 mg/kg) was 68.3%. Combination therapy produced the most obvious apoptosis effects. Compared with controls, the IRE+PDT group exhibited lower new blood vessel (VEGF, CD31), metastasis (TGF-β), and cell proliferation (Ki-67) indicators and higher inflammation indicator (TNF-α) 1 day post-treatment. Thus, combining IRE and PDT enhanced their anti-tumor effects in breast cancer, and apoptosis played a key role in this process.

BACKGROUND:Pancreatic cancer is one of the most aggressive human malignancies. The development of a novel drug to treat pancreatic cancer is imperative, and it is thought that complementary and alternative medicine (CAM) could yield such a candidate. Agaricus blazei Murrill is a CAM that has been tested as an anticancer drug, but its efficacy against pancreatic cancer is poorly understood. To study the potential of A. blazei in the treatment of pancreatic cancer, we examined the effects of its hot water extract on the proliferation and global gene expression profile of human pancreatic cancer cells.

METHODS:Three distinct human pancreatic cancer cell lines, MIAPaCa-2, PCI-35, and PK-8, and the immortalized human pancreatic duct-epithelial cell line, HPDE, were employed. The cells were incubated with the appropriate growth medium supplemented with the hot water extract of A. blazei at final concentrations of 0.005, 0.015%, or 0.045%, and cellular proliferation was assessed for five consecutive days using an MTT assay. Apoptosis was examined by using flow cytometry and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Caspase-dependent apoptosis was assayed using immunoblotting. Global gene expression profiles were examined using a whole human genome 44 K microarray, and the microarray results were validated by using real-time reverse transcription PCR.

RESULTS:The hot water extract of A. blazei significantly inhibited the proliferation of cultured pancreatic cancer cells through the induction of G0/G1 cell cycle arrest and caspase-dependent apoptosis; the effect was the smallest in HPDE cells. Furthermore, significant alterations in the global gene expression profiles of pancreatic cancer cells occurred following treatment with the hot water extract of A. blazei. Genes associated with kinetochore function, spindle formation, and centromere maintenance were particularly affected, as well as cyclins and cyclin-dependent kinases that are essential for cell cycle progression. In addition, proapoptotic genes were upregulated.

CONCLUSIONS:The hot water extract of A. blazei may be useful for the treatment of pancreatic cancer and is a potential candidate for the isolation of novel, active compounds specific for mitotic spindle dysfunction.

Although hyperbaric oxygen has been shown to enhance the efficacy of radiotherapy and chemotherapy for the treatment of several malignant tumors, the impact of hyperbaric oxygen on osteosarcoma has not yet been demonstrated. In this study, we investigated the efficacy of hyperbaric oxygen alone and in combination with an anti-cancer drug as an adjuvant to chemotherapy. In vitro, highly metastatic murine osteosarcoma cell lines were exposed to hyperbaric oxygen and cell viability was examined. Hyperbaric oxygen alone significantly suppressed cell proliferation, and hyperbaric oxygen plus carboplatin exhibited significant synergism in suppression of cell proliferation. In vivo, C3H mice were subcutaneously inoculated with osteosarcoma cells and divided into four groups: control, hyperbaric oxygen, carboplatin, and carboplatin plus hyperbaric oxygen. After 5 weeks, increase in both tumor volume and number of lung metastases was significantly suppressed in the hyperbaric oxygen group. Concomitant hyperbaric oxygen clearly enhanced the chemotherapeutic effects of carboplatin on both tumor growth and lung metastasis in osteosarcoma-bearing mice. Moreover, mortality in the carboplatin plus hyperbaric oxygen group was significantly lower than in the other three groups. These findings suggest that hyperbaric oxygen plus carboplatin combination therapy could be an appropriate therapeutic regimen for the treatment of patients with osteosarcoma.