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

• Published in: Anti-cancer agents in medicinal chemistry Vol. 24; no. 10; p. 789
• Main Authors: Shandi, Mahsa Hatami, Sahranavard, Shamim, Bagheri, Fereshteh, Shahsavari, Zahra, Salami, Siamak
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Molecular Structure; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Roots - chemistry; Reactive Oxygen Species - metabolism; Structure-Activity Relationship; Tumor Cells, Cultured; cis-platin resistant ovarian cancer; apoptosis; triple-negative breast cancer; Dorema hyrcanum; programmed cell death; Glioblastoma
• ISSN: 1875-5992
• DOI: 10.2174/0118715206273478240304095159

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. The research aimed to evaluate the cytotoxic effects of 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. Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of were investigated on cancer and normal cells by using MTT assay, and the concentration around IC values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS. Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC 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. 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 in cancer treatment with subject to further mechanistic studies.