Girija Kuttan

Anti-tumour and antioxidant activity of natural curcuminoids

Matural curcuminoids, curcumin, I, II and III isolated from turmeric (Curcuma longa) were compared for their cytotoxic, tumour reducing and antioxidant activities. Curcumin III was found to be more active than the other two as a cytotoxic agent and in the inhibition of Ehrlich ascites tumour in mice (ILS 74.1%). These compounds were also checked for their antioxidant activity which possibly indicates their potential use as anti-promoters. The amount of curcuminoids (I, II and III) needed for 50% inhibition of lipid peroxidation was 20, 14 and 11 g/m. Concentrations needed for 50% inhibition of superoxides were 6.25, 4.25 and 1.9 micrograms/ml and those for hydroxyl radical were 2.3, 1.8 and 1.8 micrograms/ml, respectively. The ability of these compounds to suppress the superoxide production by macrophages activated with phorbol-12-myristate-13-acetate (PMA) indicated that all the three curcuminoids inhibited superoxide production and curcumin III produced maximum effect. These results indicate that curcumin III is the most active of the curcuminoids present in turmeric. Synthetic curcumin I and III had similar activity to natural curcumins.

Anticancer and antioxidant activity of synthetic chalcones and related compounds

Nineteen synthetic chalcones and ten structurally related compounds were investigated for their cytotoxic, tumour reducing and antioxidant activities. Methyl and hydroxy substituted chalcones were found to be cytotoxic in vitro whereas only hydroxy substituted chalcones could reduce ascites tumour in animals. Although most of the compounds analysed showed antioxidant activity, hydroxy and methyl substituted compounds were found to be the most potent antioxidants.

Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds.

Several polyphenolic compounds were tested for the inhibition of lung metastasis induced by B16F10 melanoma cells in mice. Oral administration of polyphenols such as curcumin and catechin at concentrations of 200 nmol/kg body weight were found to inhibit the lung metastasis maximally as seen by the reduction in the number of lung tumor nodules (80%). Other polyphenols which inhibited the lung tumor nodule formation were rutin (71.2%), epicatechin (61%), naringin (27.2%) and naringenin (26.1%). The polyphenols which did not inhibit lung tumor nodule formation were quercetin, morin and ellagic acid. Consequent to the inhibition of the lung tumor nodules, the life span of animals treated with polyphenols was also found to be increased. Curcumin (143.85%), catechin (80.81%) and rutin (63.59%) had maximal increase in life span. The results indicate a possible use of these compounds in arresting the metastatic growth of tumor cells.

Anti-metastatic activity of curcumin and catechin

The inhibitory effects of curcumin and catechin on lung metastasis induced by B16F-10 melanoma cells were studied in female C57BL/6 mice. Curcumin and catechin significantly (P < 0.001) inhibited lung tumour formation (89.3% and 82.2%, respectively) and significantly increased the life span (143.9% and 80.8%, respectively). Moreover, lung collagen hydroxyproline and serum sialic acid levels were found to be significantly (P < 0.001) lower in treated animals compared to the untreated controls. Curcumin and catechin treatment (10 microg/ml) significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. Gelatin zymographic analysis of the trypsin-activated B16F-10 melanoma cells sonicate revealed that curcumin- and catechin-treated zymograms did not show any metalloproteinase activity. Curcumin and catechin treatment did not inhibit the motility of B16F-10 melanoma cells across a polycarbonate filter in vitro. These findings suggest that curcumin and catechin inhibit the invasion of B16F-10 melanoma cells by inhibition of metalloproteinases, thereby inhibiting lung metastasis.

Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice

Administration of Withania somnifera extract (Solanaceae) was found to significantly reduce leucopenia induced by cyclophosphamide (CTX) treatment. The total WBC count on the 12th day of the CTX-treated group was 3720 cells/mm3 and that of CTX along with Withania was 6120 cells/mm3. Treatment of Withania along with CTX was found to significantly (P < 0.001) increase the bone marrow cellularity (13.1 x 10(6) cells/femur) compared to CTX alone treated group (8 x 10(6) cells/femur). Administration of Withania extract increased the number of alpha-esterase positive cells (1130/4000 cells) in the bone marrow of CTX treated animals, compared to the CTX-alone treated group (687/4000 cells). The major activity of Withania somnifera may be the stimulation of stem cell proliferation. These studies indicate that Withania somnifera could reduce the cyclophosphamide induced toxicity and its usefulness in cancer therapy.

Immunomodulatory Activity of a Peptide Isolated from Viscum Album Extract (NSC 635 089)

A peptide isolated from Viscum album extract (Iscador) has been earlier reported to have cytotoxic and tumour reducing activity. Administration of the peptide (2 micrograms/ml) was found to produce increased natural killer cell activity (NK-activity) in the normal animals and tumour bearing animals. The peak activity was observed on the 3rd day after the administration of the peptide. Administration of the peptide also stimulated antibody dependent cellular cytotoxicity (ADCC) which was expressed maximally on the fourth day. There was also an increase in antibody forming cells in the spleen, and antibody titers were increased in the animals treated with the peptide. Activity of the crude plant extract coincided with the activity of the peptide, indicating that the isolated peptide is mainly responsible for the immunostimulatory activity present in Viscum album extract.

Effect of isoflavones genistein and daidzein in the inhibition of lung metastasis in mice induced by B16F-10 melanoma cells.

Two dietary soybean isoflavones, genistein and daidzein, were studied for the inhibition of lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. The isoflavone genistein at 200 mumol/kg body wt significantly inhibited (53.6%, p < 0.001) lung tumor nodule formation. The lung collagen hydroxyproline content and the serum sialic acid level, a marker of metastasis, were also significantly lower in these animals than in untreated tumor-bearing animals. Genistein treatment also increased the life span of the tumor-bearing animals (47.7%, p < 0.001). The isoflavone daidzein had no significant effect on the reduction of lung metastasis induced by B16F-10 melanoma cells.

Isolation and identification of a tumour reducing component from mistletoe extract (Iscador)

Using a combination of gel filtration and paper chromatography, a tumour reducing component from mistletoe extract (Iscador) was isolated and identified to be a peptide of approximate molecular weight 5000. The isolated peptide reduced the solid tumour induced by Daltons lymphoma ascites tumour cells (DLA cells) in mice. The isolated component was very cytotoxic to the DLA cells but was not cytotoxic to normal lymphocytes, indicating a cell dependent specificity.

Effect of a preparation from Viscum album on tumor development in vitro and in mice

The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Daltons lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.

Anti-tumour and free radical scavenging activity of synthetic curcuminoids

Abstract Eight synthetic curcuminoids were investigated for their cytotoxic and tumoricidal activities as well as for their free radical scavenging activity. All the curcuminoids were found to be cytotoxic to cultured L929 cells; concentration needed for 50% inhibition being around 1 μg/ml (3.9–2.5 μM). As antitumour agents, veratryl curcuminoid and salicyl curcuminoid increased the life span of animals by 100.6 and 86.9%, respectively. All the curcuminoids inhibited in vitro lipid peroxidation and scavenged superoxides and hydroxyl radicals. Curcuminoids with a free hydroxyl group on the phenyl ring, such as salicyl curcuminoid, were found to be most active. Compounds which did not have free hydroxyl group such as veratryl curcuminoid, had lower activity in vitro but showed comparable activity in vivo. The results indicated that synthetic curcuminoids, like natural curcumin are potent antioxidants.