britannin and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Since chemotherapy drugs have dose-related side effects, there is still a need for finding new agents with suitable cytotoxic effects without any harmful effects. For this purpose, we evaluated the cytotoxic effects of Britannin that is a Sesquiterpene Lactone compound

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Humans; Inula; Lactones; Leukocytes, Mononuclear; Phytochemicals; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sesquiterpenes; Vincristine

Britannin, a Sesquiterpene Lactone isolated from Inula aucheriana, has recently gained attraction in the therapeutic fields due to its anti-tumor properties. This study was designed to evaluate the effect of this agent on Acute Lymphoblastic Leukemia (ALL) cell lines, either as a monotherapy or in combination with Vincristine (VCR).. To determine the anti-leukemic effects of Britannin on ALL-derived cell lines and suggest a mechanism of action for the agent, we used MTT assay, Annexin-V/PI staining, ROS assay, and real-time PCR analysis. Moreover, by using a combination index (CI), we evaluated the synergistic effect of Britannin on Vincristine. We found that unlike normal Peripheral Blood Mononuclear Cells (PBMCs) and L929 cells, Britannin reduced the viability of NALM-6, REH, and JURKAT cells. Among tested cells, NALM-6 cells had the highest sensitivity to Britannin, and this agent was able to induce p21/p27-mediated G1 cell cycle arrest and Reactive Oxygen Specious (ROS)-mediated apoptotic cell death in this cell line. When NALM-6 cells were treated with Nacetyl-L-Cysteine (NAC), a scavenger of ROS, Britannin could induce neither apoptosis nor reduce the survival of the cells suggesting that the cytotoxic effect of Britannin is induced through ROS-dependent manner. Moreover, we found that a low dose of Britannin enhanced the effect of Vincristine in NALM-6 cells by inducing apoptotic cell death via altering the expression of apoptotic-related genes.. Overall, our results proposed a mechanism for the cytotoxic effect of Britannin, either as a single agent or in combination with Vincristine, in NALM-6 cells.

Topics: Acetylcysteine; Antineoplastic Agents, Phytogenic; Apoptosis; Catharanthus; Cell Survival; Drug Synergism; Free Radical Scavengers; G1 Phase Cell Cycle Checkpoints; Humans; Inula; Jurkat Cells; Lactones; Leukocytes, Mononuclear; Phytochemicals; Plant Extracts; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reactive Oxygen Species; Sesquiterpenes; Signal Transduction; Vincristine