Antioxidant, cytotoxic and apoptosis-inducing properties Carissa carandas L. against lung carcinoma cells: Insights from leaf, young & ripe fruit extracts

Abstract

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for effective therapeutic agents. Although Carissa carandas L. has demonstrated diverse biological activities, comparative evaluations of its cytotoxic potential across different plant parts against lung carcinoma are limited. This study comprehensively assessed the antioxidant, cytotoxic, and apoptosis-inducing properties of C. carandas extracts derived from leaves (CCL), young fruits (CCF-Y), and ripe fruits (CCF-R) on A549 human lung carcinoma cells. Qualitative phytochemical profiling, cell viability assays, migration inhibition, apoptosis detection, and gene expression analyses were performed. Leaf extract (CCL) exhibited the highest total phenolic content (98.65 ± 0.03 mg/g GAE) and superior antioxidant activity (IC₅₀: 2.34 ± 0.28 μg/mL), correlating with potent cytotoxic effects (IC₅₀: 11.77 ± 3.08 μg/mL), surpassing those of fruit extracts. All extracts significantly inhibited cancer cell migration and induced apoptosis through enhanced reactive oxygen species (ROS) generation and mitochondrial membrane potential disruption. Gene expression analysis of CCL-treated cells revealed marked upregulation of apoptotic markers, including caspase-9, caspase-3, and caspase-8, indicating activation of both intrinsic and extrinsic apoptotic pathways. HRLCMS revealed the presence of various phytochemicals in CCL extract. These results highlight the potential of C. carandas, particularly its leaf extract, as a valuable natural source of cytotoxic agents against lung carcinoma. Future investigations to identify and characterize the responsible bioactive phytochemicals are warranted to facilitate development of novel therapeutic compounds.