Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of
Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell
Lines
Background:
Despite remarkable advances, cancer has remained the second cause of death, which
shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of
treating diseases, and several approved chemotherapeutic compounds were isolated from plants.
Objective:
The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian,
breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is
directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production.
Methods:
Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum
were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was
used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR
and production of ROS.
Results:
Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions
showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF
cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death
in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased
in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively
in A2780CP cells after 30 minutes and up to 24 hours.
Conclusion:
Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The
methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells.
Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action
were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings
suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic
studies.
