An isolate "CD
lignan mixture" comprising
lignans from stem wood of Cedrus deodara consisted of (-)-wikstromal (75 - 79%), (-)-
matairesinol (9 - 13%) and benzylbutyrolactol (7 - 11%) and was studied for its in vitro cytotoxicity against human
cancer cell lines. The in vivo anticancer activity of CD
lignan mixture was studied using Ehrlich
ascites carcinoma and colon
carcinoma (CA-51) models in mice. Its effect was also studied on
annexin V binding, intracellular
caspases and DNA fragmentation to gain insight into the mode of action. In vitro cytotoxicity studies showed significant dose-dependent effects against several
cancer cell lines from different tissues such as breast, cervix,
neuroblastoma, colon, liver, and prostate
at 10, 30 and 100 microg/mL. The IC (50) values varied from 16.4 ng/mL to 116.03 microg/mL depending on the cell line. Comparative data of IC (50) values of CD
lignan mixture showed a synergistic effect in comparison to the individual molecules, i. e., (-)-
matairesinol, (-)-
wikstromol present in CD
lignan mixture . CD
lignan mixture had the most pronounced effect on CNS cell lines followed by colon. The
tumor regression observed with Ehrlich
ascites carcinoma and CA-51 was 53% and approximately 54%, respectively, when CD
lignan mixture was given at 300 mg/kg, I. P. for nine days in the Ehrlich
ascites carcinoma model and 400 mg/kg, I. P. for the same period in the CA-51 model. It was comparable with
5-fluorouracil at 22 mg/kg and 20 mg/kg, respectively. CD
lignan mixture
at 10, 30 and 100 microg/mL increased the percentage of
annexin V positive HL-60 cells to 1.9 - 17.18% as compared to control (1.04%). In K562 cells CD
lignan mixture
at 10, 30 or 100 microg/mL and
staurosporine (1 microM) showed 9.13%, 11.38%, 17.22% and 28.07% intracellular
caspases activation, respectively. A distinct
DNA laddering pattern was observed for treatment with the CD
lignan mixture in HL-60, K562 (30 microg/mL and 100 microg/mL) and MOLT-4 cells (30 microg/mL) after 24 h incubation.
DNA cell cycle analysis indicated that CD
lignan mixture
at 10, 30 and 100 microg/mL increased the content of hypodiploid (sub G(1) phase) cells when compared to control (2.55, 5.4 and 6.25% vs. 0.27%). The present study indicates that CD
lignan mixture has cytotoxic potential against human
cancer cell lines. It has the ability to induce
tumor regression in vivo. It induces apoptosis as indicated by
annexin V positive cells, induction of intracellular
caspases, DNA fragmentation and
DNA cell cycle analysis.