Cryptolepine Analog Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway.

BACKGROUND: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. OBJECTIVE: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. METHODS: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. RESULTS: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. CONCLUSION: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.

Nanotechniques Inactivate Cancer Stem Cells.

One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.In this study, the ability of synthesized hybrid nanocomplexes, comprising the nanoparticles of rare earth orthovanadates GdYVO4:Eu3+ and cholesterol to inhibit the tumor growth and to increase the survival of the animals with tumors was established. A special contribution into tumor-inhibiting effect is made by each of its components. Treatment of Ehrlich carcinoma cells with two-component hybrid complex resulted in maximum reduction in the concentration of the most tumorigenic CD44high cells with simultaneous rise in the number of CD117+ cells that decreased an intensity of tumor growth by 74.70 ± 4.38% if compared with the control.

Effects of Antitumor Agents to DNA Synthesis in the Gastric Epithelia of Mice Implanted with Ehrlich Carcinoma Cells: An Autoradiographic Study / 대한해부학회지

This experiment was performed to evaluate the morphological responses of the gastric epithelium of the mouse, inoculated with Ehrlich carcinoma cells, following administration of 5-fluorouracil, adriamycin or mitomycin C. Healthy adult ICR mice weighing 25 gm each were divided into normal control and experimental groups (tumor control group, 5-fluorouracil treated group, adriamycin treated group, and mitomycin C treated group). In the experimental groups, each mouse was inoculated with 1 x 10(7) Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), adriamycin (2 mg/kg) or mitomycin C (400 microgram/kg) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of anticancer drugs, each mouse was injected with a single dose of 0.7 microCi/gm of methyl-3H-thymidine (25Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On histological study, in the gastric mucosae of adriamycin-treated groups, denatured surface epithelial cells, expanded lumen of the gastric gland, and congested lamina propria were observed. But in the 5-fluorouracil or mitomycin treated groups, severe morphological changes of the gastric mucosae were not observed. On autoradiographic study, numbers of the labeled cells in the gastric mucosae per 3.5 mm length of normal control, tumor control, 5-fluorouracil-treated, adriamycin-treated and mitomycin C treated groups were 267.3 (+/-48.86), 273.6 (+/-59.41), 375.3 (+/-83.36), 15.3 (+/-9.66) and 124.0 (+/-32.66), respectively. In the adriamycin and mitomycin C-treated group, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control group. But in the 5-fluorouracil-treated group, number of the heavy labeled cells were observed more frequently than in those of the normal control group. From the above results, adriamycin and mitomycin C may severely suppress the DNA synthesis of the epithelial cells of the gastric mucosae. But some amount of the 5-fluorouracil (30 mg/kg) may not suppress the DNA synthesis of gastric epithelial cells.

Effects of Adriamycin or CP-2 to the Rectal Mucosae of Mouse Implanted with Ehrlich Carcinoma Cells: An Autoradiographic Study / 대한해부학회지

This experiment was performed to evaluate the morphological responses of the rectal intestinal glands of the mouse, inoculated with Ehrlich carcinoma cells, following administration of adriamycin or composition of the extracts of the Croton tiglium and Coptis chinensis rhizome (CP-2, Institute of Experimental Tumor Research, Seoul, Korea). Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group, adriamycin treated group, and CP-2 treated group). In the experimental groups, each mouse was inoculated with 1 x 10(7) Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day, 0.2 mL of saline, adriamycin (2 mg/kg) or CP-2 (30 mg/kg) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of anticancer drugs, each mouse was injected with a single dose of 0.7 microCi/gm of methyl- 3H-thymidine through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed. and rectal tissues were collected and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in the dark room and dried. The number of the labeled epithelial cells of the rectal crypts (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On histological study, in the rectum of adriamycin treated groups, length of the intestinal crypts is shorter than those of the normal control ones. Disrupted intestinal crypts and epithelial cells were observed. But in the CP-2 treated group, morphological changes of the rectum were not observed. On autoradiographic study, number of the labeled cells of normal control, rumor control, adriamycin-treated, CP-2-treated groups were 263.1 (+/-38.65), 395.7 (+/-52.52), 73.3 (+/-22.54), 96.3 (+/-28.36), respectively. In the adriamycin and CP-2 treated groups., poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently than in those of the normal and tumor control groups. But in the tumor control group, number of the heavy labeled cells were observed more frequently than in those of the normal control group. From the above results, adriamycin and CP-2 may suppress the DNA synthesis of the cells of the rectal crypts. But CP-2 does not result any histological defect on the rectal mucosa. These results suggest that CP-2 is expected as one of most effective anticancer drugs.