14-Deoxy-11,12-didehydroandrographolide inhibits proliferation and induces GSH-dependent cell death of human promonocytic leukemic cells.

Abstract

14-Deoxy-11,12-didehydroandrographolide (AND2), an analogue of andrographolide, showed more potent cytotoxicity against human promonocytic leukemia (THP-1) cells than adherent cancer cell lines. In this study AND2 was isolated from the plant Andrographis paniculata and it was characterized. The antiproliferative effect of AND2 on both adherent (PC-3 and MDAMB) and non-adherent (THP-1 and Jurkat) cancer cell lines was evaluated by MTT assay. The effect of intracellular reduced glutathione (GSH) on AND2-induced cytotoxicity was studied by conducting cell viability assays on GSH-pretreated cells. The effect of AND2 on the redox status of THP-1 cells was determined by analyzing the endogenous reduced GSH content. Apoptosis induction was confirmed by DNA laddering assay and Western blot analysis using anti-caspase-3 protein antibody. AND2 showed antiproliferative action on both THP-1 and Jurkat cancer cell lines with low IC50 values. Cytotoxicity of AND2 was reversed by GSH pretreatment. AND2 treatment decreased the GSH content by 19.76 % (p < 0.001) in the THP-1 cancer cell line and reduced the cell clumping between the THP-1 cells. Expression of procaspase-3 varied in THP-1 cells during the time course of AND2 treatment. Procaspase-3 expression reached a maximum in treated cells at 32 h and was markedly reduced at 48 h but no procaspase-3 cleavage was observed. The obtained results suggest that AND2 is more effective against leukemia cells. AND2 induced a redox-mediated cell death in THP-1 cells. As AND2 temporarily increased the procaspase-3 expression during treatment, this study encourages the preclinical testing of AND2 against promonocytic leukemia cells in combination with small molecules that directly activate procaspase-3 to caspase-3.

• Authors: Rahul Raghavan, Sanith Cheriyamundath, Joseph Madassery
• Journal: Journal of natural medicines (J Nat Med) Vol. 68 Issue 2 Pg. 387-94 (Apr 2014) ISSN: 1861-0293 [Electronic] Japan
• PMID: 24458985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-deoxy-11,12-didehydroandrographolide
• Antineoplastic Agents
• Diterpenes
• Caspase 3
• Glutathione

Topics

• Andrographis (chemistry)
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Diterpenes (chemistry, pharmacology, toxicity)
• Glutathione (metabolism)
• Humans
• Jurkat Cells
• Leukemia (drug therapy, enzymology, metabolism)