A novel carissic acid from fruits of Carissa carandas induced apoptotic cell death in A-549 cells following the activation of caspases

Abstract

This study was designed to identify cytotoxic compounds from Carissa carandas extract. The cytotoxic activity of extract and fractions were assessed against eight cancer cell lines. The chloroform fraction obtained from methanolic extract exhibited significant activity against MCF-7, HT-29, A-549 with IC₅₀ values of 3.98 µg/mL (MCF-7), 1.28µg/mL (HT-29) and 1.48 µg/mL (A-549) respectively. Further investigation led to the isolation of novel compound carissic acid (CA), which was confirmed by detailed spectroscopy studies. CA exhibited notable activity with IC₅₀ values of 3.47 µM for A-549, 2.65 µM for HT-29 and 13.58 ± 0.59 µM for MCF-7 cells. CAcaused chromatin condensation with decrease of mitochondrial membrane potential and also confirmed cell death via Reactive Oxygen Species (ROS) generation and significantly decreased the colony formation in dose-dependent manner. The overall findings suggested that CA demonstrates cytotoxic effect by inhibiting cell proliferation and promoting apoptosis in lung (A-549) carcinoma cell line.

Graphical Abstract

Keywords:

• Carissa carandas
• SRB assay
• carissic acid
• apoptosis
• A-549
• HT-29

Acknowledgements

The authors are thankful to CSIR-IIIM, Jammu for providing the research facilities, Regional Research Sub-Station for Sub-Tropical Fruits, Raya, SKUAST-Jammu for providing the fruit material and UGC for providing the fellowship to NK, during the research period.

Disclosure statement

There are no conflicts to declare

Additional information

Funding

This work was partially supported by the CSIR, New Delhi (Grant No. HCP-010 and SERB EMR/2016/002586). It bears IIIM Communication No. IIIM/2161/2023.