Antitumor effects of chitin specific lectin from Praecitrullus fistulosus by targeting angiogenesis and apoptosis.

In the present study, chitin specific lectin was purified from fruit exudates of Praecitrullus fistulosus. The lectin was purified and analyzed using affinity chromatography, RP-HPLC and electrophoretic studies. Furthermore, protein was identified by MALDI-MS/MS and peptide mass fingerprinting. Purified lectin (PfL) effectively agglutinates RBC, lymphocytes and displayed strong cytotoxicity against colon cancer (line HT29) cells among screened cells. PfL induced apoptosis by altering the expression of apoptotic proteins via caspadse-3 dependent pathway. In vivo studies using EAC mice model proves the efficacy of PfL by activating apoptosis and inhibiting the tumor neovasculature by targeting the MVD, VEGF and MMP's secretion. More importantly, the PfL treatment leads to effective inhibition of tumor growth and a ∼2.71 fold increase in the lifespan of EAC mice. Collectively, our study provides comprehensive evidence that the role of dietary lectins with significant cytotoxic potential by targeting tumor angiogenesis and activating apoptosis in cancer study models.

In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor.

In the present study, four novel dienone cyclopropoxy curcumin analogs 1a-4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a-4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a-4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance.

In vivo tumor inhibitory and radiosensitizing effects of an Indian medicinal plant, Plumbago rosea on experimental mouse tumors.

Tumor growth inhibitory and radiosensitizing effects of the alcoholic root extract of P. rosea was studied on experimental mouse tumors, S-180 solid tumor and Ehrlich ascites carcinoma in vivo. Intraperitoneal injection of 50 mg/kg of Plumbago extract (PE) for 10 days starting from 24 hr after intradermal inoculation of S-180 cells in BALB/c mice produced about 16% complete response (CR). The CR% increased with increase in drug dose, to 50% at 100 mg/kg for 10 days. As 100 mg/kg produced toxic side effects, lower doses were used with other treatment modalities, radiation (RT) and hyperthermia (HT). Treatment of 50 mm3 tumor with PE (75 mg/kg) for 10 days with local RT (10 Gy) and/or HT (43 degrees C, 30 min) subadditively increased the CR% and tumor free survival. The combination also significantly reduced the growth rates of uncured tumors. The PE significantly reduced the tumor glutathione content and this effect was markedly enhanced by the combination of the three modalities. PE alone was not very effective in preventing the growth of Ehrlich ascites carcinoma in Swiss mice, though it increased mean survival time and ILS% of the mice. But with radiation it produced a synergistic effect in increasing the tumor inhibition and 120 day animal survival from 10% to 50%. The results demonstrate that though PE may have only a weak antitumor effect, it may be a good candidate for use with radiation to enhance the tumor killing effect.

Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180.

Antitumor and radiosensitizing effects of alcoholic root extract of W. somnifera and their modification by heat were studied in vivo on Sarcoma-180 grown on the dorsum of adult BALB/c mouse. Ashwagandha (AT) was injected (ip) at a dose of 500 mg/kg body wt for 10 consecutive days into mouse bearing tumor of 50 +/- 5 mm3, with or without a local treatment of 10 Gy gamma radiation (RT) or hyperthermia at 43 degrees C for 30 min (HT) or both on 5th day of AT. The response was assessed on the basis of tumor regression, growth delay, animal survival and changes in the tumor GSH content. Ashwagandha, RT and HT individually produced 18, 38 and 45% complete response (CR) respectively, but RT gave the best long term survival. Ashwagandha increased the effect of radiation on tumor regression as well as growth delay, but AT + HT gave a better tumor cure. However, both these combinations gave almost identical long term survival, which was not much higher than that produced by RT alone. The combination of Ashwagandha for 10 days with one local exposure to RT followed by HT significantly increased the tumor cure, growth delay of partially responding tumors and animal survival. This combination also significantly and synergistically depleted the tumor GSH level, with no recovery even at 3 hr after treatment. It is concluded that Ashwagandha, in addition to having a tumor inhibitory effect, also acts as a radiosensitizer and heat enhances these effects. The severe depletion in the tumor GSH content by the combination treatment must have enhanced the tumor response, as the inherent protection by the thiol will be highly reduced.

Toxic effects of crude root extract of Plumbago rosea (Rakta chitraka) on mice and rats.

The ethanolic root extract of Plumbago rosea (Plumbaginaceae) was studied for acute toxicity in mice and subacute toxicity in rats. The 24 h LD50 values of the extract in mice were 239.88 mg and 1148.15 mg/kg b.wt. for intraperitoneal and oral routes, respectively. Oral administration of doses above 1250 mg/kg produced severe diarrhea. In subacute toxicity studies no mortality was observed when 50 mg/kg of the extract was injected i.p. daily for 30 days; however, there was no weight gain in the treated rats. Significant reduction in the weights of liver, kidney, thymus and testes was observed in the male rats, while the spleen weight showed a significant increase from control. The females showed a significant loss in thymus weight and a gain in the weight of the uterus, but the liver and spleen did not show any weight change from the control. There was a significant increase in total WBC and neutrophil counts as well as in the levels of serum alkaline phosphatase and alanine transaminase (ALT) in both sexes. Similarly, the liver alkaline phosphatase level was significantly higher than control, but a significant reduction was observed in the DNA, RNA and total proteins. Thus, a higher drug dose (total dose of 15 g/kg b.wt.) was tolerated in fractionated administration, but it had a growth inhibitory effect in both sexes. The males appear to be more susceptible than females when individual organs are considered.

In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma 180.

Withania somnifera is a medicinal plant used in the treatment of a variety of ailments in the Ayurvedic system. Alcoholic extract of the root of the plant was injected(ip) at daily doses of 200 to 1000 mg/kg body wt for 15 days starting from 24 hr after intradermal inoculation of 5 x 10(5) cells of S-180 in BALB/c mice. Solid tumor growth was monitored for 100 days. Doses of 400 mg/kg and above produced complete regression of tumor after an initial growth, the percentage of complete response (CR) increasing with increasing drug dose. A 55% CR was obtained at 1000 mg/kg drug administration, but this dose also produced some mortality among the animals. A significant increase in the volume doubling time and growth delay was seen when the drug dose was increased from 500 to 750 mg/kg body wt, but further increase in drug dose to 1000 mg/kg did not produce any significant increase in these responses. Cumulative doses of 7.5 to 10 g at daily doses of 500 or 750 mg/kg seems to produce a good response in this tumor.