Abstract
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 cytotoxcity 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 prostrate at 10, 30 and 100 μg/mL. The IC50 values varied from 16.4 ng/mL to 116.03 μg/mL depending on the cell line. Comparative
data of IC50 values of CD lignan mixture showed a synergistic effect in comparision 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
∼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 μg/mL increased
the percentage of annexinV 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 μg/mL and staurosporine
(1 μM) showed 9.13 %, 11.38 %, 17.22 % and 28.07 % intacellular caspases activation,
respectively. A distinct DNA laddering pattern was observed for treatment with the
CD lignan mixture in HL-60, K562 (30 μg/mL and 100 μg/mL) and MOLT-4 cells (30 μg/mL)
after 24 h incubation. DNA cell cycle analysis indicated that CD lignan mixture at
10, 30 and 100 μg/mL increased the content of hypodiploid (sub G1 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.
Key words
Cedrus deodara
- Pinaceae - cytotoxicity - apoptosis - anti-tumor
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shashankksingh@gmail.com
