Abstract
Purpose: Breast cancer is an important public health problem worldwide. Natural compounds derived from plants have emerged as promising candidates for fighting cancer due to their safety, minimal toxicity, and potential effectiveness. This study investigated the apoptotic effect of the ethanol extract of Lycopodium clavatum on SKBR-3 human breast cancer cells.
 Materials and Methods: The effect of applying Lycopodium clavatum ethanol extract at different doses (100, 200, and 300 µg/mL) and duration (12, 24, and 48 hours) to evaluate the viability of human breast cancer cells was investigated using the WST-1 cytotoxicity test. Also, the mechanism of apoptosis of Lycopodium clavatum ethanol extract was investigated by intrinsic (BAX and Caspase-9) and extrinsic (Caspase-8 and Caspase-3) pathways.
 Results: The application of Lycopodium clavatum ethanol extract had a cytotoxic effect on SKBR-3 cells and this effect was dependent on the dose and duration of treatment. After 12 hours of incubation with LC-EE, 10%, 25%, and 40% cell death were observed in the 100, 200, and 300 µg/mL groups, respectively, compared to the control group. Additionally, our findings demonstrate that Lycopodium clavatum treatment induces the stimulation of apoptotic proteins, including BAX, Caspase-9, Caspase-8, and Caspase-3.
 Conclusion: The anti-cancer effect of Lycopodium clavatum ethanol extract in SKBR-3 cells was determined by activating intrinsic and extrinsic apoptotic pathways. These findings suggest that Lycopodium clavatum may assist in the development of new therapeutic strategies as an effective anti-cancer agent against human breast cancer.
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