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Dioscorea deltoidea Leaf Extract (DDLE) Targets PI3K/AKT/mTOR Pathway and Inhibits Ovarian Cancer Cell Growth
Ying Jiao1, Ying Xiong2, Lin He1
1Department of Gynecology, The No. 2 Hospital of Baoding, 071000, Baoding, Hebei, China.
Abstract:
Ovarian cancer is the malignant tumour of the female reproductive organ with highest mortality rate among all the types of gynaecological tumours. This study investigated the effect of Dioscorea deltoidea leaf extract (DDLE) on OV-90 and CAOV4 ovarian cancer cells. The results demonstrated that DDLE suppresses OV-90 and CAOV3 cell viability significantly in dose dependent manner. The OV-90 and CAOV3 cell viability were reduced to 24 and 27% respectively with 20 mg/mL DDLE treatment. Five mg/mL DDLE treatment of OV-90 and CAOV4 cells raised percentage of cells in G2-phase to 55.9 and 51.2%, respectively. In 5 mg/mL DDLE -treated OV-90 and CAOV4 cells a prominent suppression in cyclin-D1 and cyclin B1 proteins was observed in 48 h. The DDLE treatment promoted OV-90 and CAOV3 cell apoptosis to 34.65 and 29.89%, respectively. The Fas, FasL, cleaved caspase-3, and Bax levels were up-regulated markedly in the cells after DDLE treatment. Moreover, DDLE treatment suppressed p-mTOR, p-AKT and p-PI3K expression in OV-90 and CAOV3 cells. Thus, DDLE suppressed ovary cancer cell viability and elevated cell apoptosis. Inhibitory effect of DDLE on ovarian cancer cells is associated with targeting PI3K/AKT/mTOR pathway.
Insights
Dioscorea deltoidea leaf extract (DDLE) effectively inhibits ovarian cancer cell growth and promotes apoptosis. This natural compound targets the PI3K/AKT/mTOR pathway, offering a potential therapeutic strategy for ovarian cancer.
Area of Science:
- Oncology
- Pharmacology
- Phytochemistry
Background:
- Ovarian cancer presents the highest mortality rate among gynecological malignancies.
- Exploring novel therapeutic agents from natural sources is crucial for effective ovarian cancer treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of Dioscorea deltoidea leaf extract (DDLE) on ovarian cancer cell lines.
- To elucidate the molecular mechanisms underlying DDLE's inhibitory action on ovarian cancer cells.
Main Methods:
- In vitro study using OV-90 and CAOV4 ovarian cancer cell lines.
- Assessment of cell viability, cell cycle progression, protein expression (cyclins, apoptosis markers, PI3K/AKT/mTOR pathway components), and apoptosis induction.
Main Results:
- DDLE significantly reduced ovarian cancer cell viability in a dose-dependent manner.
- DDLE induced G2-phase arrest and suppressed key cell cycle proteins (cyclin-D1, cyclin B1).
- DDLE promoted apoptosis by upregulating Fas, FasL, cleaved caspase-3, and Bax, while downregulating p-mTOR, p-AKT, and p-PI3K.
Conclusions:
- DDLE exhibits potent anti-ovarian cancer activity by inhibiting cell proliferation and inducing apoptosis.
- The mechanism involves the targeted suppression of the PI3K/AKT/mTOR signaling pathway.
- DDLE represents a promising natural compound for further development as an ovarian cancer therapeutic.
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