Background: Antibiotics are commonly used in cancer patients for the treatment of infectious disease which is the most frequent and life-threatening complication. Little is known whether antibiotics can affect cancer development and chemotherapy. We aimed to assess the influence of commonly used antibiotics on the proliferation of cancers and on conventional chemotherapy.Methods: 9 human cancer cell lines were used for proliferation study in vitro. The anticancer activity of 5 commonly used antibiotics in hospitals, levofloxacins, cephalosporins, penicillin, streptomycin, and metronidazole, were assessed. Cisplatin and 5-fluorouracil were used as conventional chemotherapeutic drugs. Tumor growth retardation effects were observed in animals implanted with nasopharyngeal carcinoma with the administration of levofloxacin or combination of levofloxacin and cisplatin.Findings: Levofloxacin showed much stronger anticancer effects than other antibiotics on all cancers, except anticancer effect of cephalosporins on nasopharyngeal carcinoma. The anticancer effects of levofloxacin were dose- and time- dependent in vitro. The anticancer effects of levofloxacin also occurred in vivo. Relative tumor volume (RTV), relative proliferation ratio (RPR), tumor weight (TW) in levofloxacin group were markedly less than those in vehicle control group. Levofloxacin synergistically enhanced the chemotherapy of cisplatin in all cancers both in vitro and in vivo. RTV, RPR and TW in combination group were only 4.74 folds, 39.16% and 0.86g respectively; significantly less than 12.11 folds, 100% and 2.01g in vehicle control group (p<0.05); 8.57 folds, 70.75% and 1.84g in levofloxacin group (p<0.05); and 6.63 folds, 54.70% and 1.25g in cisplatin group.Interpretation: Levofloxacin is broad-spectrum and effective anticancer antibiotic; very good sensitizer of chemotherapy; and the best choice of antibiotics in the prevention and treatment of bacterial infectious disease in cancer patients. It can be used either alone or concomitantly with chemotherapy. Levofloxacin can greatly influence clinical practice in cancer treatment.Funding: National Natural Science Foundation of China.Declaration of Interest: We declare no competing interests.Ethical Approval: Animal work described in this manuscript has been proved by the Ethical Committee of Kunming Medical University, Yunnan province, China.
Glioma is the most common malignant brain tumor and the patients are prone to poor prognosis. Due to limited treatments, new drug exploration has become a general trend. Therefore, the objective of this study is to investigate the effect of the new drugs C18H17NO6 and its combination with Scutellarin on glioma cells and the underlying mechanism.U251 and LN229 cells were administrated with C18H17NO6 and its combination with Scutellarin. The proliferation ability of glioma cells was determined by cell counting kit-8, plate clone formation assay, and EdU incorporation assay. The cell cycle and apoptosis detection were detected by flow cytometry. Moreover, TUNEL assay was also used for cell apoptosis analysis. Then, the transfer ability of cells was achieved through wound healing assay. Furthermore, polymerase chain reaction (PCR) test and western bolt analysis were used to detect the mRNA expression and protein expression, respectively. Lastly, immunofluorescence was for the purity identification of astrocyte.The results showed that, with the increasing dose of C18H17NO6, the cell inhibition rate, the cells in G1 phase, and the apoptosis rate were gradually increased, but the clone number, proliferation rate, and the cells in G2 and S phases were gradually decreased in comparison with control group. However, with the increase of C18H17NO6, the transferred rate of U251 and LN229 was not significantly augmented, expect that on U251 in C18H17NO6 5 μM group. In addition, Scutellarin 200 μM has little effect on proliferation, with the inhibition rate 10-20% and proliferation rate except U251 in Scutellarin 200 μM group similar to that in control group. Moreover, compared to control group, Scutellarin 300 μM increased the U251 cells in G2 and S phases and the apoptosis rate of LN229 but decreased the LN229 cells in G2 and S phases. Besides, in Scutellarin 200 μM group, the transfer ability of LN229 was inhibited, but not in U251. Furthermore, if C18H17NO6 was combined with Scutellarin 200/300μM, the proliferation and transferred ability were suppressed and the apoptosis was elevated in LN229 cell in comparison with C18H17NO6 alone. Dramatically, the combined effect on U251 was the exact opposite. Importantly, there was little toxicity on astrocyte under the dose of C18H17NO6 and Scutellarin in the study. In molecular level, the mRNA and protein expression of Fas-associated factor 1 (FAF1) expression in U251 and LN229 were upregulated by C18H17NO6 and its combination with Scutellarin, especially the protein expression.C18H17NO6 could efficiently suppress cell proliferation and induce cell apoptosis in glioma cells, and its combination with Scutellarin had a promoting effect, in which the underlying mechanism referred to the upregulation of Fas-associated factor 1.
One cost-effective way for identifying novel cancer therapeutics is in the repositioning of available drugs for which current therapies are inadequate. Levofloxacin prevents DNA duplication in bacteria by inhibiting the activity of DNA helicase. As eukaryotic cells have similar intracellular biologic characteristics as prokaryotic cells, we speculate that antibiotics inhibiting DNA duplication in bacteria may also affect the survival of cancer cells. Here we report that levofloxacin significantly inhibited the proliferation and clone formation of cancer cells and xenograft tumor growth through cell cycle arrest at G2/M and by enhancing apoptosis. Levofloxacin significantly altered gene expression in a direction favoring anticancer activity. THBS1 and LAPTM5 were dose-dependently upregulated whereas SRD5A3, MFAP5 and P4HA1 were downregulated. Pathway analysis revealed that levofloxacin significantly regulated canonical oncogenic pathways. Specific network enrichment included a MAPK/apoptosis/cytokine-cytokine receptor interaction pathway network that associates with cell growth, differentiation, cell death, angiogenesis and development and repair processes and a bladder cancer/P53 signaling pathway network mediating the inhibition of angiogenesis and metastasis. THBS1 overlapped in 16 of the 22 enriched apoptotic pathways and the 2 pathways in the bladder cancer/P53 signaling pathway network. P4HA1 enriched in 7 of the top 10 molecular functions regulated by differential downregulated genes. Our results indicate that levofloxacin has broad-spectrum anticancer activity with the potential to benefit cancer patients already treated or requiring prophylaxis for an infectious syndrome. The efficacy we find with levofloxacin may provide insight into the discovery and the design of novel less toxic anticancer drugs.
BACKGROUND Osteosarcoma (OS) is a highly aggressive, metastatic bone tumor with a poor prognosis, and occurs more commonly in children and adolescents. Therefore, new drugs and treatments are urgently needed. In this study, we investigated the effect and potential mechanisms of C₁₈H₁₇NO₆ on osteosarcoma cells. MATERIAL AND METHODS Human MNNG osteosarcoma cells were treated with different concentrations of C₁₈H₁₇NO₆. The proliferation of the MNNG cells was examined via CCK-8 assay. Cell migration and invasion were tested via wound-healing assay and Transwell migration and invasion assays. ELISA was used to detect MMP-2, MMP-9, and VEGF secretion. Finally, Western blotting and qRT-PCR were used to detect protein and mRNA expressions, respectively. RESULTS C₁₈H₁₇NO₆ inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C₁₈H₁₇NO₆ treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C₁₈H₁₇NO₆ inhibited tumor growth in a MNNG xenograft. We also found that C₁₈H₁₇NO₆ can significantly reduce the phosphorylation of the PI3K/AKT signaling pathway in vivo and in vitro. However, 740Y-P (a PI3K agonist) had the opposite effect on proliferation, migration and invasion of MNNG cells treated with C₁₈H₁₇NO₆. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C₁₈H₁₇NO₆. CONCLUSIONS Our results suggest that C₁₈H₁₇NO₆ can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C₁₈H₁₇NO₆ may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.
This study compared the effects of three anti-mutagenic lichen extracts on colorectal oncogenesis in azoxymethane (AOM)-treated mice and determined whether the extracts also regulated the homeostatic response to genotoxic damage. C57BL/6J mice (n = 12 per group) were treated with the lichen extracts Antimutagen-He (AMH): AMH-C, AMH-D, or AMH-E dimethyl sulfoxide (DMSO, control) for 2 weeks. At the end of the treatment, mice were given a single AOM injection to induce DNA damage and killed 6 h later for measuring apoptosis and proliferation. Apoptotic and proliferation indexes in mice treated with AMH-C, AMH-D, and AMH-E were 0.61%, 1.41%, and 0.77%; and 30.62%, 21.93%, and 27.27%, respectively, which were significantly lower than those of control mice (5.88% and 38.69%) (p < 0.05). To examine the effects of lichen extracts on colorectal cancer, separate groups of mice (n = 25 per group) treated with AMH-C, AMH-D, AMH-E, or DMSO were given 4-weekly AOM injections to induce oncogenesis. Mice were killed 24 weeks after the last AOM injection for assessing colon tumor formation. Colonic tumor incidences were 47.3%, 13%, and 20%; the tumor volumes were 18.47, 2.75, and 10.78 mm3, respectively, in mice treated with AMH-C (p < 0.05), AMH-D (p < 0.05), and AMH-E (p > 0.05), compared to 24% and 13.28 mm3 in mice of control correspondingly. No lichen extract showed evident toxic effects on mice. No usnic acid was found in these lichen extracts. The regulation of acute apoptosis and cell proliferation in colonic epithelial cells and the anti-mutagenesis do not seem directly related to the cancer protective effect.
Faecal pH and cholate are two important factors that can affect colon tumorigenesis, and can be modified by diet. In this study, the effects of two Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on the pH and the cholic acid content in feces, in addition to colon tumorigenesis, were studied in mice. Kunming mice were randomized into various groups; negative control group (NCG), azoxymethane control group (ACG), pork oil group (POG), and canola oil Ggroup (COG). Mice in the ACG were fed a basic rodent chow; mice in POG and COG were given 10% cooking oil rodent chow with the respective oil type. All mice were given four weekly AOM (azoxymethane) i.p. injections (10 mg/kg). The pH and cholic acid of the feces were examined every two weeks. Colon tumors, aberrant crypt foci and organ weights were examined 32 weeks following the final AOM injection. The results showed that canola oil significantly decreased faecal pH in female mice (P<0.05), but had no influence on feces pH in male mice (P>0.05). Pork oil significantly increased the feces pH in both male and female mice (P<0.05). No significant change was found in feces cholic acid content when mice were fed 10% pork oil or canola oil compared with the ACG. Although Kunming mice were not susceptible to AOM-induced tumorigenesis in terms of colon tumor incidence, pork oil significantly increased the ACF number in male mice. Canola oil showed no influence on ACF in either male or female mice. Our results indicate that cooking oil effects faecal pH, but does not affect the faecal cholic acid content and thus AOM-induced colon neoplastic ACF is modified by dietary fat.
Pharmacognosy Research,2020,12,1,40-46.DOI:10.4103/pr.pr_70_19Published:February 2020Type:Original ArticleAuthors:Wen-Jing Lian, Xiao-Qiong He, Qian Yao, Zhong-Yu Song, and Jing Wang Author(s) affiliations:Wen-Jing Lian1, Xiao-Qiong He1, Qian Yao2, Zhong-Yu Song2, Jing Wang3 1School of Public Health, Kunming Medical University, Yunnan Province, 650500, CHINA. 2Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Province, 650500, CHINA. 3Physical Examination Center, The Second Affiliated Hospital of Xi'an Medical University, Shanxi Province, 710038, CHINA. Abstract:Background: Lethariella cladonioides, also known as Red Snow Tea and Golden Silk Tea, mainly grows in Tibet, Sichuan and Yunnan of China. Its medicinal value has been gradually discovered. Objectives: This study mainly evaluated the anti‑cancer effect of AMH‑L extracted from L. cladonioides in vitro and in vivo and to explore its anticancer mechanism. Materials and Methods: MTT assay was used to determine the cytotoxicity of AMH‑L to human cancer cells A‑549 and HCT‑116 in vitro. Sarcoma S‑180 and human lung cancer NCL‑H460 cells were implanted into Kunming mice and Balb/C nude mice, respectively, anti‑cancer activity in vivo was assessed by recording body weight, organ coefficient and tumor inhibition rate. Flow cytometry and western blotting were used to preliminarily explore the anticancer mechanism. Results: AMH‑L, the active component of Red Snow Tea, had strong anticancer activity against A‑549 and HCT‑116, and IC50 was 26.17 ± 3.54 and 16.21 ± 0.83. When the dosage was 50, 100 and 150 mg/ kg, the inhibition rates of S‑180 in Kunming mice were 36.04%, 43.14%, and 50.45% in turn, respectively. At the end of the experiment, the dose was 150, and the relative proliferation inhibition rate of Balb/C nude mice NCI‑H460 tumor was 50.36%. Cell cycle and apoptotic results showed that AMH‑L could block A‑549 at G2/M phase and promote apoptosis of HCT‑116 by inducing poly (ADP‑ribose) polymerase lysis. Conclusion: L. cladonioides extract AMH‑L exhibits strong anticancer activity in vivo and in vitro and can be used as a potential anticancer drug for further study. Keywords:Anticancer drug, Apoptosis, Cell cycle, Cleaved poly (ADP‑ribose) polymerase, LichenView:PDF (2.57 MB)
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