Therapeutic potential of xanthones from Swertia chirata in breast cancer cells

Abstract

Background & objectives : Medicinal plants like Swertia chirata are rich sources of different xanthones. This study was aimed to assess the cytotoxic potential of four most abundant xanthones present in S. chirata both in vivo and in vitro in Ehrlich ascites carcinoma (EAC), a mouse transplantable breast carcinoma cell line and two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). Methods : Four xanthones derived from S. chirata namely 1-hydroxy-3,7,8-trimethoxyxanthone (XA), 1,8-dihydroxy-3,5-dimethoxyxanthone (XB), 1-hydroxy-3,5,8-trimethoxyxanthone (XC) and 1,5,8-trihydroxy-3-methoxyxanthone (XD) were used for determination of sub-lethal dose on the cell lines EAC, MCF-7, MDA-MB-231 and verified toxicity of sub-lethal dose on normal murine fibroblast cells. Cytotoxicity was measured in vivo and survivability of mice was plotted accordingly. Therapeutic efficacy of XD was evaluated both in vivo and in vitro by determination of lipid peroxidation (LPO), reactive oxygen species (ROS) generation and by quantitating the enzyme status (GSH, catalase, superoxide dismutase) in treated and untreated samples. DNA damage was evaluated using comet and DNA fragmentation assays. Furthermore, apoptotic effect was analyzed by flow cytometry and validated by TUNEL assay and Western blotting. Results : Among all the xanthones tested XD showed IC 50 at the lowest dose, and normal cells were unaffected at this dose. Survivability of mice increased significantly when treated with XD compared to other xanthones and cisplatin. Significantly increased ROS and LPO were found in cancer cells as a result of XD treatment which was unaltered in normal cell line. XD induced DNA damage and apoptosis in cancer cell lines. Interpretation & conclusions : Our experimental data indicate that XD may potentially act as a chemotherapeutic agent by enhancing ROS in breast cancer cells thereby leading to apoptosis.

Biochemical characterization of bioinspired nanosuspensions from Swertia chirayita extract and their therapeutic effects through nanotechnology approach

“…A study revealed that a dosage of xanthone (1 and 5 M) derived from S. chirayita was helpful against cancer (EAC) and identified three major compounds from cells, MCF-7 and MDA-MB-231 cell lines without damaging the normal cells (fibroblast) [ 36 ]. Another investigation reported that ZnO-NPs synthesized from S. chirayita extract exhibit significant cytotoxic activity against cancer cells.…”

Metallo-protease Peptidase M84 fromBacillus altitudinisinduces ROS dependent apoptosis in ovarian cancer cells by targeting PAR-1

“…The effects of 3.0 µg/ml of Peptidase M84 were compared against control groups, where mice were randomised in six different groups as mentioned earlier. After 45 days and 60 days of tumour inoculation, mice were sacrificed to collect total cells from the peritoneum and cells viability was checked by trypan blue exclusion method as described previously by Barua et al , 2020 [57].…”