Methanolic Extract of Costus pictus D. DON Induces Cytotoxicity in Liver Hepatocellular Carcinoma Cells Mediated by Histone Deacetylase Inhibition

Pharmacogn Mag. 2017 Oct;13(Suppl 3):S533-S538. doi: 10.4103/pm.pm_524_16. Epub 2017 Oct 11.

Abstract

Background: Leaves of Costus pictus D. Don, (insulin plant) are used as dietary supplement for the treatment of diabetes.

Objective: The antidiabetic activity of this plant is well documented, but its activity on different cell types and mechanism remains unknown. Thus, the present study evaluates the cytotoxicity of C. pictus methanolic extract (CPME) against various cancer and normal cells.

Materials and methods: Dried leaves of C. pictus were extracted using methanol and were subjected to histone deacetylase (HDAC) inhibition and toxicity studies.

Results: The CPME displayed a selective toxicity toward tested cancer cells in a dose- and time-dependent manner. CPME exhibited significant cytotoxicity on Liver hepatocellular carcinoma cells (Hep G2) (half maximal inhibitory concentration IC50 = 6.7 mg/ml). Since CPME demonstrates both antidiabetic, anticancer activity, and HDAC enzyme play a detrimental role in both the complications, we have evaluated the CPME-induced HDAC regulation on Hep G2 cell lines. CPME showed a notable HDAC inhibition (55%). Furthermore, CPME did not show any genotoxicity or membrane instability at the tested concentrations.

Conclusion: CPME demonstrates selective cytotoxicity toward tumor cells at a lower concentration through HDAC inhibition.

Summary: C. pictus is used as munching supplementary food for the treatment of diabetesCPME selectively induces cytotoxicity in cancer cells leaving normal cells healthySelective toxicity to cancer cells are attributed by the inhibition of HDAC enzymeCPME did not show any genotoxicity and membrane instability in blood cellsCPME could be potential source of HDAC inhibitor. Abbreviations used: A549: Human lung carcinoma cells, CPME: Costus pictus methanolic extract, DMEM: Dulbecco's modified eagle's medium, DMSO: Dimethyl sulfoxide, ELISA: Enzyme-linked immunosorbent assay, 5-FU: 5-Fluorouracil, Hep G2: Liver hepatocellular carcinoma cells, HEK-293: Human embryonic kidney cells, Hela: Human cervical carcinoma cells, HT-29: Human colorectal adenocarcinoma cells, HDAC: Histone deacetylase, IC50: Half maximal inhibitory concentration, MCF-7: Human breast adenocarcinoma cells, MDA-MB-435S: Human breast cancer cells, MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, NFF: Neonatal foreskin fibroblasts, PHA: Phytohemagglutinin, PBS: Phosphate buffer saline, RPMI-1640: Roswell Park Memorial Institute Medium.

Keywords: Costus pictus methanolic extract; cytotoxicity; histone deacetylase; liver hepatocellular carcinoma cells.