Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells
Background: Nowadays, remarkable attention has been drawn towards the effective therapeutic characteristic of natural products targeting cancerous cells. This study aimed to investigate the anti-cancer effect of Artemisia annua extract (AAE), a Chinese herbal medicine alone and in combination with a microtubule binding agent used in ALL treatment, vincristine (VCR), in B-Acute lymphoblastic leukemia (ALL) Nalm-6 and Reh cells.
Materials and Methods: Cytotoxic activity of AAE and VCR was determined using MTT assay in Nalm-6, and Reh cell lines and synergism was evaluated using the CompuSyn software. Caspase 3 activity and Annexin/PI staining were performed for apoptosis assessment. The expression level of apoptosis-related genes, caspase 3, Bax and Bcl-2 were determined using real time-PCR. One-way ANOVA and post hoc Tukey multiple comparisons were used for statistical analysis.
Results: Our findings revealed that a single administration of AAE exerted an anti-leukemic effect in both ALL-derived cells in a time- and dose-dependent manner. Interestingly, the growth inhibitory activity of the extract was more potentiated when combined with 0.1 and 1 nM VCR through caspase 3-dependent apoptosis. Moreover, real-time PCR analysis showed that VCR-induced cytotoxicity was augmented by AAE through alteration of Bax, and Bcl-2 mRNA expression.
Conclusion: Overall, owing to the nontoxic nature of AAE and its explicit role in enhancing VCR effectiveness, our study provided new insight into the development of a novel combinatorial approach in ALL using natural herbs. The practical implication of the research requires further investigation through clinical trials, opening avenues for forthcoming treatment improvements.
2. Dehghan-Nayeri N, Eshghi P, Pour KG, et al. Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia. Cancer Chemother. Cancer Chemother Pharmacol. 2017; 80(1):177-185.
3. Nikbakht M, Jha AK, Malekzadeh K, et al. Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population. Exp Oncol. 2017; 39(1): 57-64
4. Arpe ML, Rørvig S, Kok K, et al. The association between glucocorticoid therapy and BMI z-score changes in children with acute lymphoblastic leukemia. Support Care Cancer. 2015; 23(12):3573-80.
5. Bahmani F, Esmaeili S, Bashash D, et al. Centaurea albonitens extract enhances the therapeutic effects of Vincristine in leukemic cells by inducing apoptosis. Biomed Pharmacother. 2018; 99:598-607.
6. Chao MW, Lai MJ, Liou JP, et al. The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. J Hematol Oncol. 2015; 8:82.
7. Lahlou M. The success of natural products in drug discovery. Pharmacol Pharm. 2013; 4(3A):17-31.
8. Yang Y, Zhang Z, Li S, et al. Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis. Fitoterapia. 2014; 92:133-47.
9. Mucciarelli M, Maffei M. Introduction to the genus. Taylor and Francis, London, UK; 2002. p. 1-50.
10. Tan RX, Tang HQ, Hu J, et al. Lignans and sesquiterpene lactones from Artemisia sieversiana and Inula racemosa. Phytochemistry. 1998; 49(1):157-61.
11. Bora KS, Sharma A. The genus Artemisia: a comprehensive review. Pharm Biol. 2011; 49(1):101-9.
12. Tayarani-Najaran Z, Hajian Z, Mojarrab M, et al. Cytotoxic and apoptotic effects of extracts of Artemisia ciniformis Krasch and Popov ex Poljakov on K562 and HL-60 cell lines. Asian Pac J Cancer Prev. 2013; 15(17):7055-9.
13. Taghizadeh Rabe SZ, Mahmoudi M, Ahi A, et al. Antiproliferative effects of extracts from Iranian Artemisia species on cancer cell lines. Pharm Biol. 2011; 49(9):962-9.
14. Fox JM, Moynihan JR, Mott BT, et al. Artemisinin-derived dimer ART-838 potently inhibited human acute leukemias, persisted in vivo, and synergized with antileukemic drugs. Oncotarget. 2016; 7(6):7268-79.
15. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001; 29(9):e45.
16. Yin S-Y, Wei W-C, Jian F-Y, et al. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med 2013; 2013.pp???
17. Cao P, Cai X, Lu W, et al. Growth inhibition and induction of apoptosis in SHG-44 glioma cells by Chinese medicine formula “Pingliu Keli”. Evid Based Complement Alternat Med. 2011; 2011.pp???
18. Foo JB, Saiful Yazan L , Tor YS, et al. Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway. J Ethnopharmacol. 2015; 166:270-8.
19. Singh NP, Ferreira JF, Park JS, et al. Cytotoxicity of ethanolic extracts of Artemisia annua to Molt-4 human leukemia cells. Planta Med. 2011; 77(16):1788-93.
20. Worku N, Mossie A, Stich A, et al. Evaluation of the in vitro efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk extracts in cancer and Trypanosoma brucei cells. ISRN Biochem. 2013; 2013:910308.
21. Kim EJ, Kim GT, Kim BM, et al. Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells. BMC Complement Altern Med. 2017; 17(1):236.
22. Darvishi M, Esmaeili S, Dehghan-Nayeri N, et al. Anticancer effect and enhancement of therapeutic potential of Vincristine by extract from aerial parts of Juniperus excelsa on pre-B acute lymphoblastic leukemia cell lines. J Appl Biomed.2015; 15(3):219-226.
|Issue||Vol 13, No 3 (2019)|
|Acute lymphoblastic leukemia; Vincristine; Extract; Apoptosis; Cytotoxicity|
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