Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
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Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Hindawi Publishing Corporation
Abstract
Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia
plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of
Polyalthia longifolia (MEP) with potent activity against human leukemia cells. In the present study, we evaluated the efficacy of
MEP against prostate cancer (PCa) and established the molecular basis of its effect in in vitro and in vivo models. We observed
that MEP treatment resulted in a significant decrease in the growth and viability of PCa cells, associated with arrest in the G1/S
phase of the cell cycle. Apoptosis was confirmed as the primary mode of MEP-induced cell death through activation of the
intrinsic apoptotic machinery. Proteomic and biochemical studies identified BiP as an important target of MEP with the
activation of the ER stress pathway, as a potential mechanism driving MEP-induced apoptosis. The extract exhibited strong
efficacy in the PCa xenograft mouse model with significant inhibition of tumor growth and reduced tumor burden. Taken
together, our findings indicate that MEP-induced apoptosis in PCa cells concomitant with the activation of the ER stress
pathways results in the inhibition of tumor growth, in vitro and in vivo. Our studies provide initial evidence of the efficacy of
MEP against PCa and advocate for in-depth studies in other preclinical models for its possible use in clinical settings.
Description
Keywords
Antioxidant properties, Polyalthia longifolia
Citation
11. Afolabi, S.O., Olorundare, E.O., Babatunde, A., Albrecht R.M., Koketsu, M., Syed, D.N., & Mukhtar, H. (2019). Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies. Oxidative Medicine and Cellular Longevity, Volume 2019, Article ID 6726312, 14 pages