Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

Abstract

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.

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“…for the NALM6 cell line was 1.83 nM (Figure 1C). These values are in concordance with other reports (Darvishi et al, 2017;Mashati et al, 2019) and were used in all subsequent experiments. Next, we evaluated whether exposure to BPA, BADGE, or PFOA at concentrations of 1 and 10 nM could have a protective effect against VCR-induced cytotoxicity.…”

Phytochemical Composition and In Vitro Antioxidant, Anti-Inflammatory, Anticancer, and Enzyme-Inhibitory Activities of Artemisia nilagirica (C.B. Clarke) Pamp

“…In comparison, the standard cyclophosphamide was more toxic to these cells, with respective IC 50 values of 3.12 ± 0.13, 5.74 ± 0.20, and 6.04 ± 0.21 µg/mL. Previous studies have also shown different species of Artemisia in various cancer cells [ 47 , 48 , 49 , 50 ]. In addition, the green synthesized nanoparticles from different Artemisia species are also reported to exert antiproliferative effects on cancer cells mediated through apoptotic cell death [ 23 , 51 , 52 ].…”

Recent Developments in Search of Effective Herbal Medicine for The Treatment of Leukemia

“…The latter showed considerable cytotoxicity when AAE was used alone or combined with Vincristine. Thus, suggesting that using AAE in conjunction with Vincristine would allow for lower Vincristine concentrations, leading to lesser general toxicity in ALL treatment [19]. Nevertheless, more research in a clinical context could help to confirm the ALL's efficacy and assess the usefulness of this strategy.…”

“…In addition, the extract upregulated caspase-3 and Bax, the essential genes engaged in the apoptotic signaling, accompanied by an apparent inhibitory action on the transcriptional action of the antiapoptotic gene, Bcl-2. As a result, AAE increased Vincristine caused cytotoxic effects by modifying Bax and Bcl-2 mRNA expression [19].…”