| dc.description.abstract | Piper crocatum Ruiz & Pav. (red betel) is a medicinal plant known for its
antioxidant and anticancer properties. However, its apoptosis-inducing activity
associated with mitochondrial dysfunction and its antiproliferative effects against
A549 human lung cancer cells remain insufficiently explored. This study aimed to
evaluate the phytochemical composition, antioxidant activity, apoptosis-inducing
potential, antiproliferative activity, and molecular interactions of P. crocatum
extract and fractions. Leaves of P. crocatum were extracted with 70% ethanol and
fractionated into n-hexane, ethyl acetate, and aqueous fractions. Phytochemical
constituents, including phenolics, flavonoids, and alkaloids, were determined, and
antioxidant activity was evaluated using the DPPH assay. Apoptosis-like activity
was assessed in Saccharomyces cerevisiae through petite-frequency and rhodamine
B fluorescence assays, while antiproliferative activity against A549 lung cancer
cells was determined using the MTT assay. In addition, LC-MS-identified
phytochemicals were subjected to multi-target molecular docking against EGFR,
BCL-2, and KRAS G12C to investigate their potential molecular interactions.The
ethyl acetate fraction exhibited the highest phytochemical contents and strong
antioxidant activity. In yeast, the crude extract at 10 ppm induced the highest petite
frequency and the greatest reduction in rhodamine B fluorescence, indicating
pronounced mitochondrial dysfunction and apoptosis-like induction. The ethyl
acetate fraction also showed the strongest antiproliferative activity against A549
cells, with an IC50 of approximately 111 ppm. Molecular docking demonstrated that
several compounds, particularly Vitexin 2''-O-ß-L-rhamnoside, Kaempferitrin,
Vitexin, Flemiphilippinin, and Fusarin C, exhibited favorable binding affinities
toward EGFR, BCL-2, and KRAS G12C, suggesting their potential to regulate
multiple pathways involved in cancer progression and apoptosis.Overall, the
findings demonstrate that P. crocatum possesses significant antioxidant, apoptosis
inducing, and antiproliferative activities. The integration of in vitro experiments
with in silico multi-target molecular docking provides mechanistic insight into its
anticancer potential and supports the development of P. crocatum as a promising
natural source of multitarget anticancer agents. | |
