Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines

Title:Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines

Volume: 24 Issue: 10

Author(s): Mahsa Hatami Shandi, Shamim Sahranavard*, Fereshteh Bagheri, Zahra Shahsavari and Siamak Salami

Affiliation:

• Traditional Medicine and Materia Medical Research Center, Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran

Keywords: Glioblastoma, triple-negative breast cancer, cis-platin resistant ovarian cancer, apoptosis, programmed cell death, Dorema hyrcanum.

Abstract:

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.

Cite this article as:

Shandi Hatami Mahsa, Sahranavard Shamim*, Bagheri Fereshteh, Shahsavari Zahra and Salami Siamak, Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2024; 24 (10) . https://dx.doi.org/10.2174/0118715206273478240304095159