Inhibitory effect of cinnamoyl compounds against human malignant cell line.

In the present study, anti-proliferative effects of dietary polyphenolic compounds have been observed and demonstrated the strong anticancer efficacy of curcumin (CMN), an active constituent of dietary spice (turmeric) using human leukemia cancer cell line. CMN inhibited the proliferation of K562 leukemic cells by induction of apoptosis. The current study demonstrated synergy with combination of drug therapy, and suggested that combination of ferulic acid and cisplatin synergistically inhibited cellular proliferation. Cytotoxic synergy was observed independent of the sequence of addition of two drugs to cultured cells. The synergized growth inhibitory effect with cisplatin was probably associated with G2-M arrest in cell cycle progression. These findings suggested that among the cinnamoyl compounds, CMN was most potent and FER appeared to be a better modulating agent on human malignant cell line.

Efficacies of plant phenolic compounds on sodium butyrate induced anti-tumour activity.

The ability of the differentiation inducing agent sodium butyrate (NaB) alone or combined with plant-derived phenolic compounds to produce growth inhibition in human erythroleukemic cells was investigated. As a single agent, curcumin produced a marked inhibition of proliferation indicated by its low concentration used. The effect of phenolics on the cell cycle could probably contribute to the augmented antiproliferative activity of NaB. The present data show that quercetin produced synergistic effect in terms of cell killing in association with NaB. Both curcumin and ferulic acid potentiated NaB-induced reduction of cell number. When NaB was added before exposure to graded doses of quercetin it did induce a greater inhibitory effect. The combination of NaB and quercetin seems less effective on S180 ascites tumour cells. As a single agent quercetin was found to be the most efficacious on S180 tumour model.

Cell death by apoptosis and cancer chemotherapy.

The ways by which cell death takes place have generated great interest in recent years particularly in the field of cancer. The exact mechanisms which are responsible for tumour regression by drug treatment are also largely unknown and involve both enhanced cell death and arrested cell proliferation. Cell death is caused either by necrosis or by an active process in response to a specific stimulus which leads to elimination of a definite proportion of cells. This process of programmed cell death is referred to as apoptosis (a term coined by developmental biologists) and is a part of the morphogenetic processes, characterized by shrinkage of cells, condensation of nuclear chromatin, nuclear fragmentation and blebbing. Many successful cancer treatments presently undertaken depend upon induction of an apoptotic response in the target tumour cells. As apoptosis is considered to be an active gene-directed process, in tumours the precise mode of cell death after chemotherapy is important. Understanding the role of apoptosis in cancer will greatly broaden our knowledge of all stages of the disease process and its treatment. Thus, the role of apoptotic response modulation during the generation of neoplasia is an important issue and will remain an active area of present day investigations for improving the efficiency of chemotherapy. It is likely to become a valuable weapon in the war against cancer.

Efficacy of 5-fluorouracil in combination with methoxyphenyl maleamic acid in murine tumors.

Combination chemotherapy studies were carried out in vivo against sarcoma 180 (ascites)(S180) and Ehrlich (ascites) carcinoma (EAC) tumours using cytotoxic drugs and methoxyphenyl maleamic acid (MPMA), an intermediate in the synthesis of pyrrolidine-nitrogen-mustards. Preliminary data have suggested that the combination of 5-fluorouracil (5-FU) and methoxyphenyl maleamic acid (MPMA) was more active than 5-FU used singly against EAC tumour. The possible therapeutic potential of this combination was further investigated in EAC tumour.

Methoxyphenyl maleamic acid augments the activity of cytotoxic drugs against murine tumours.

The anti-tumour effects of methoxyphenyl maleamic acid (MPMA) and cytotoxic drugs, in combination were investigated on P388 leukaemia and S180 (ascites) tumours. Simultaneous administration of MPMA with CTX or HN2 resulted in enhancement of anti-tumour activity. The increased activity was observed against P388 leukaemia, whereas S180 (ascites) tumour was not responsive to the combined treatment. The possible mechanism (s) of action, responsible for the modulation of activity of CTX and HN2 against P388 tumour have been postulated.

Combined effect of cyclophosphamide and extracts of Crotalaria and Senecio plants on experimental tumours.

The combined effect of cyclophosphamide (CTX) and extracts of six patients belonging to Crotalaria and Senecio genera was assessed on experimental transplantable S180 (both ascitic and solid forms) tumour. Successive petroleum ether and methanolic extracts from these plants were obtained. The combined administration of CTX and petroleum ether extract of C. albida and the methanolic extracts of C. albida, S. chrysanthemoides, S. densiflorus and S. jacquemontianus led to prolonging the life span of S180 (ascitic) tumour bearing mice. The data indicate that the most effective extract in combination with CTX was the methanolic extract of S. chrysanthemoides. The extracts alone had no effect on survival of tumour-bearing mice. The same extracts and the same combinations had no effect on S180 solid tumour.

Cytotoxicity of the acetylated oil of Semecarpus anacardium Linn. f.

The cytotoxic effects of acetylated oil of Semecarpus anacardium nuts on the cells of P388 lymphocytic leukemia were tested in vitro. The product was tested at the concentrations ranging from 15-75 micrograms/ml. The cell kill was observed as early as three hr after the treatment. The effects of acetylated oil on the biosynthesis of DNA, RNA and protein using labelled thymidine, uridine and leucine respectively showed that the product inhibited the biosynthesis of all the three. This was indicated by the inhibition of the incorporation of their precursors. The uptake of 3H-thymidine was inhibited 15 min after treatment; while that of 3H-uridine and 14C-leucine took 30 and 45 min respectively. Since the S. anacardium oil was unstable due to air-oxidation, the studies were confined to its acetylated product.

Anti tumour and pharmacological effects of the oil from Semecarpus anacardium Linn. f.

Semecarpus anacardium Linn.f. nuts were extracted by using non-polar and polar organic solvents. Hot methanol extract and a resinous fraction, isolated from it, showed antitumour activity against P388 lymphocytic leukaemia in BDF1 mice as judged by their median survival time. Petroleum ether extract and its chromatographically isolated fraction were obtained. The latter fraction was distilled under reduced pressure to get an orange-coloured oil, (b.p. 200-20 degrees/2-3 mm). Both had antitumour activity. The orange-coloured oil, on further distillation under reduced pressure, yielded Bhilawanol. An acetyl derivative of the oil was also obtained. The latter two also had antitumour activity.