Chebulinic Acid Isolated From the Fruits of Terminalia chebula Specifically Induces Apoptosis in Acute Myeloid Leukemia Cells

Abstract

Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL-60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines. Chebulinic acid treatment to HL-60 and NB4 cells induced caspase activation, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, chromatin condensation, and changes in the mitochondrial membrane permeability. Additionally, inhibition of caspase activation drastically reduced the chebulinic acid-induced apoptosis of acute promyelocytic leukemia cells. Our data also demonstrate that chebulinic acid-induced apoptosis in HL-60 and NB4 cells involves activation of extracellular signal-regulated kinases, which, when inhibited with ERK inhibitor PD98059, mitigates the chebulinic acid-induced apoptosis. Taken together, our findings exhibit the selective potentiation of chebulinic acid-induced apoptosis in acute promyelocytic leukemia cells. Copyright © 2017 John Wiley & Sons, Ltd.

Development of response surface methodology for optimization of parameters and quantitative analysis of chebulinic acid from composition of medicinal herbs by HPLC

“…This method studies revealed that 0.712% w/w of chebulinic acid content in the composition of herbal powder, the assay of chebulinic acid was calculated according to Eq. (4) (Chhabra et al, 2017). The retention time observed for the authentic sample of chebulinic acid results was given in Fig.…”

Chebulinic acid inhibits MDA‐MB‐231 breast cancer metastasis and promotes cell death through down regulation of SOD1 and induction of autophagy

“…We found that incremental doses of CA induced concomitant cell death in MDA‐MB‐231 cells. Although, CA has previously been demonstrated to have cytotoxic properties against a variety of cancer cell lines namely leukemia, vascular smooth muscle cells, pancreatic cancer, prostate cancer, and osteosarcoma cell lines (Chhabra et al, 2017; Saleem, Husheem et al, 2002; Shi et al, 2008), our study extends anticancer activity of CA to highly metastatic cancer types and provides a molecular basis for its activity by identifying its ability to induce autophagy and downregulating SOD1 as putative molecular target. CA treatment induced significant cell death and reduced proliferative and metastatic characteristics in TNBC's.…”

“…MDA‐MB‐231 cell line was procured from American Type Culture Collection and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) with antibiotics and maintained in a humidified incubator with 5% CO 2 at 37°C. Isolation and validation of CA was performed as previously described (Chhabra et al, 2017). Stock of CA was prepared at the concentration of 50 mM in DMSO.…”

“…The cells were harvested, washed twice with 1X PBS, and resuspended in PBS. Changes in membrane potential are measured by a fluorescence emission shift from green (~529 nm) to red (~590 nm) by using Becton Dickinson FACS Calibur (Chhabra et al, 2017).…”

“…Additionally, CA also displays anti‐migration activity inhibiting smooth muscle cell migration (Song, Jeong, Park, Shim, & Jang, 2017). Although many studies have been carried out with regard to the effects of CA in cancer including our previous report in myeloid leukemia cells (Chhabra et al, 2017), very few studies have concentrated on highly aggressive and metastatic forms like TNBCs.…”