Effects of crude extracts from medicinal herbs Rhazya stricta and Zingiber officinale on growth and proliferation of human brain cancer cell line in vitro.

Ayman I Elkady,Rania Abd El Hamid Hussein,Osama A Abu-Zinadah

doi:10.1155/2014/260210

Abstract

Hitherto, limited clinical impact has been achieved in the treatment of glioblastoma (GBMs). Although phytochemicals found in medicinal herbs can provide mankind with new therapeutic remedies, single agent intervention has failed to bring the expected outcome in clinical trials. Therefore, combinations of several agents at once are gaining increasing attractiveness. In the present study, we investigated the effects of crude alkaloid (CAERS) and flavonoid (CFEZO) extracts prepared from medicinal herbs, Rhazya stricta and Zingiber officinale, respectively, on the growth of human GBM cell line, U251. R. stricta and Z. officinale are traditionally used in folkloric medicine and have antioxidant, anticarcinogenic, and free radical scavenging properties. Combination of CAERS and CFEZO treatments synergistically suppressed proliferation and colony formation and effectively induced morphological and biochemical features of apoptosis in U251 cells. Apoptosis induction was mediated by release of mitochondrial cytochrome c, increased Bax : Bcl-2 ratio, enhanced activities of caspase-3 and -9, and PARP-1 cleavage. CAERS and CFEZO treatments decreased expression levels of nuclear NF-κBp65, survivin, XIAP, and cyclin D1 and increased expression level of p53, p21, and Noxa. These results suggest that combination of CAERS and CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of GBM.

Highlights

Glioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm, accounting for more than half of all brain tumors, and is among the most lethal phenotypes of all cancers
We found a lower IC50 value of combination of 40 μg/mL CAERS and 40 μg/mL CFEZO than combination of 20 μg/mL CAERS and 20 μg/mL CFEZO (Figure 1), we did not want to continue with the combination of 40 μg/mL CAERS and 40 μg/mL CFEZO that showed too much cytotoxicity as we found in the in situ Wright staining
The analysis revealed an increase in Bax expression and a decrease in Bcl-2 expression indicating that CAERS and/or CFEZO treatments tipped balance of Bax : Bcl-2 ratio in favor of apoptosis

Summary

Introduction

Glioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm, accounting for more than half of all brain tumors, and is among the most lethal phenotypes of all cancers. The poor prognosis of those patients is owing to the intrinsic resistance of the GBM cells to apoptosis [2]. Induction of apoptosis in glioblastoma cells has come to be appreciated as targets for the management of GBM [3]. Apoptosis is a highly sophisticated and elaborate mode of cell death that requires precise regulation of different intracellular signaling pathways to ensure the continuation of the transmission of the death signal. The typical executioners of apoptosis are intracellular cysteine proteases called caspases, stored in most cells as zymogens or procaspases [5]. These caspases are activated by two pathways: the death receptor (extrinsic) and mitochondrial (intrinsic) pathways. The mitochondrial pathway initiates apoptosis in most physiological and pathological situations and is triggered by a variety of apoptotic stimuli, which converge at the mitochondria, leading to the release

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