Curcumin Induces Autophagy Associated G₁ Cell Cycle Arrest in Spodoptera frugiperda Sf9 Cells

Curcumin, a plant-polyphenolic compound, has been reported to induce autophagy and autophagic cell death in insect cells but its impact on cell cycle regulation is not well understood. In this study, we investigated the short-term effects of curcumin on the cell proliferation, cell cycle progression and autophagy-associated cellular responses in the Sf9 insect cells of Spodoptera frugiperda. Short-term treatment of Sf9 cells with low-dose curcumin (5-15 µg/mL) resulted in a continuous decrease in cell proliferation in a dose and time dependent manner. Flow cytometric analysis showed a significant increase in the number of cells in the G 1 phase, indicating G 1 cell cycle arrest. This was also supported by nuclear morphology analysis using DAPI staining. Importantly, the growth inhibition caused by curcumin was not associated with apoptotic features or DNA fragmentation. Treatment with curcumin evoked a time-dependent increase in intracellular reactive oxygen species without significant mitochondrial membrane depolarization, indicating a controlled stress response instead of mitochondrial-dependent apoptosis. Scanning electron microscopy revealed significant surface morphological remodeling including cell shrinkage and membrane irregularities consistent with structural reorganization associated with autophagy. Molecular docking analysis using conserved insect cell cycle regulatory proteins supported a potential interaction of curcumin with G₁ phase cyclin-dependent kinases. Taken together, the findings demonstrate that curcumin induces autophagy-linked G₁ cell cycle arrest in Sf9 cells, extending previous observations of curcumin-induced autophagy and nucleophagy. This study highlights autophagy-mediated cell cycle regulation as a key mechanism underlying curcumin-induced growth suppression in insect cells and provides insight into the cellular actions of botanical bioactive compounds relevant to insect physiology.