Original Article

Cytotoxic and apoptogenic activity of Bryonia aspera extract on pre-B acute lymphoblastic leukemia cell lines


Background: The natural products and conventional chemotherapeutic drug combinations are believed to increase cure rates of anticancer treatment while reducing its toxicity. The current study investigates cytotoxic and apoptogenic effects of methanolic extract of Beryonia aspera, and also synergistic effects of this extract and Prednisolone on acute lymphoblastic leukemia cell lines.
Materials and Methods: The under study populations were NALM-6 and REH cell lines. Cells were treated by Prednisolone and B. aspera extract alone and in combination. The effect of the drugs on survival and apoptosis were examined using MTT and flow cytometry, respectively. Moreover, the effects of the drugs on the mRNA expression levels of Bax and Bcl-2 were studied using RQ-PCR. Finally, both the transcriptional and enzymatic activity of caspase-3 were investigated by caspase-3 assay kit.
Results: The B. aspera extract induced cell growth inhibition and triggered apoptosis in a dose- and time-dependent manner. Real-time PCR analysis of apoptotic target genes revealed that this agent shifted the ratio of the death promoter to death repressor genes via alteration of Bax and Bcl-2 expression levels. These changes resulted in caspase-3 activation, which led to DNA fragmentation and subsequent apoptosis. Our study has also demonstrated that the combined treatment of B. aspera extract with Prednisolone did not induce greater cytotoxic effect as compared to treatment series using either Prednisolone alone.
Conclusion: Our study demonstrated that the B. aspera extract has anti-leukemic properties on BCP-ALL cell lines and could be regarded as a promising agent for the treatment of ALL.

Safa M, Tavasoli B, Manafi R, et al. Indole-3-carbinol suppresses NF-κB activity and stimulates the p53 pathway in pre-B acute lymphoblastic leukemia cells. Tumor Biol. 2015; 36(5):3919-30.

Bhojwani D,Yang JJ, Pui CH. Biology of childhood acute lymphoblastic leukemia. Pediatr Clin North Am. 2015; 62(1):47-60.

Rahman M, Hirabayashi Y, Ishii T, et al. Prednisolone sodium succinate down-regulates BSAP/Pax5 and causes a growth arrest in the Nalm6 pre-B cell line. Tohoku J Exp Med. 2001;193(3):237-44.

Lambrou GI, Vlahopoulos S, Papathanasiou C, et al. Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression. Leuk Res. 2009; 33(12):1684-95.

Schäcke H, Döcke W-D, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(1):23-43.

Ghaderi S, Falahati hosein abad A, Sarailoo MH, et al. Investigation of the components and antibacterial effects of three plant's essential oil Coriandrum sativum, Achilleh millefolium, Anethum graveolens in vitro. J Shahrekord Univ Med Sci. 2012; 14(5): 74-82

Robinson MM, Zhang X. The world medicines situation 2011. 3rd edition. Genava. World Health Organization. 2011. 1-4.

Cragg GM, Newman DJ, Snader KM. Natural products in drug discovery and development. Journal of natural products. 1997 Jan 22; 60(1):52-60.

Sahranavard S, Naghibi F, Ghffari S. Cytotoxic activity of extracts and pure compounds of Bryonia aspera. Int J Pharm Pharmaceut Sci. 2012;4(3):541-3.

Esmaeili S, Naghibi F, Mosaddegh M, et al. Screening of antiplasmodial properties among some traditionally used Iranian plants. J Ethnopharmacol. 2009; 121(3):400-4

Pourgonabadi S, Amiri MS, Mousavi SH. Cytotoxic and apoptogenic effects of Bryonia aspera root extract against Hela and HN-5 cancer cell lines. Avicenna J Phytomed. 2017; 7(1):66-72.

Jiang N, Kham SK, Koh GS, et al. Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL). J Proteomics. 2011; 74(6):843-57

Millar BC, Bell JB, Hobbs S, et al. Lymphotoxic activity of methyl prednisolone in vitro—I: Comparative toxicity of methyl prednisolone in human cell lines of B and T origin. Biochem Pharmacol. 1987;36(6):831-7.

Carmichael J, DeGraff WG, Gazdar AF, et al. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987; 47(4):936-42.

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.

Bashash D, Ghaffari SH, Zaker F, et al. BIBR 1532 increases arsenic trioxide-mediated apoptosis in acute promyelocytic leukemia cells: therapeutic potential for APL. Anti-Cancer Agents Med Chem. 2013; 13(7):1115-25.

Shoeb M. Anticancer agents from medicinal plants. Bangladesh J pharmacol. 2006; 1(2):35-41.

Efferth T, Li PC, Konkimalla VS, et al. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 2007; 13(8):353-61.

Tissing WJ, den Boer ML, Meijerink JP, et al. Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells. Blood. 2007;109(9):3929-35.

Bunz F. Cell death and cancer therapy. Current Opinion in Pharmacology. 2001;1(4):337-41.

Kerr J. A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Pathol Bacteriol. 1965;90(2):419-35.

Wang K, Yin XM, Chao DT, et al. BID: a novel BH3 domain-only death agonist. Genes Dev. 1996; 10(22):2859-69.

Benarba B, Meddah B, Aoues A. Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt's lymphoma cells. J Ethnopharmacol. 2012; 141(1):510-6.

Moghe AS, Gangal SG, Shilkar PR. In vitro cytotoxicity of Bryonia laciniosa (Linn.) Naud. on human cancer cell lines. Indian Journal of Natural Products and Resources.2011; 2(3):322-329.

IssueVol 12, No 3 (2018) QRcode
SectionOriginal Article(s)
Acute lymphoblastic leukemia Bryonia aspera Prednisolone Apoptosis Combination therapy

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How to Cite
Yazdanpanah S, Esmaeili S, Bashash D, Dehghan Nayeri N, Esfini Farahani M, Gharehbaghian A. Cytotoxic and apoptogenic activity of Bryonia aspera extract on pre-B acute lymphoblastic leukemia cell lines. Int J Hematol Oncol Stem Cell Res. 2018;12(3):203-211.