Abstract
Resistance to chemotherapy and recurrence are major hurdles to treating hormone receptor-negative breast cancer. The crude extract and natural products obtained from medicinal plants are believed to be multitargeted and possess less toxicity as compared to synthetic compounds. The aerial parts and roots of Moricandia sinaica (Boiss.) Boiss were used to prepare the crude extracts in solvents of different polarities. Human breast cancer cell lines (MCF7 and MDA-MB-231), liver carcinoma (HepG2), and nontumorigenic cells of human origin (human umbilical vein endothelial cells (HUVEC)) were treated with a serial dilution of crude extracts obtained from the aerial and roots of Moricandia sinaica (Boiss.) Boiss. The methanol extract of the shoots exhibited a higher level of cytotoxicity against MDA-MB-231 cells than against any other cancer and nontumorigenic cells lines. Six new compounds were identified by gas chromatography–mass spectrophotometry analysis in the shoots extract of Moricandia sinaica (Boiss.) Boiss, and 2-Tridecen-1-ol was one of the major compounds that represent more than 35% of the extract. M-phase inducer phosphases 1 and 2 (CDC 25A and B) were identified as the specific protein target for 2-Tridecen-1-ol by the Swiss protein target prediction tool. In silico molecular docking showed the binding of 2-Tridecen-1-ol with CDC 25 B with a higher binding energy as compared to CDC 25A. The possible molecular mechanism of anticancer activity of Moricandia sinaica (Boiss.) Boiss in MDA-MB-231 breast cancer is through inhibition of M-phase inducer phosphatases 1 and 2 via 2-Tridecen-1-ol. Further investigations in breast cancer models are needed to explore the therapeutic potential of Moricandia sinaica (Boiss.) Boiss and 2-Tridecen-1-ol as an efficient remedy with a possibly less toxic approach to treat triple-negative breast cancer.
Highlights
Breast cancer is a predominant cancer among women [1], and over 2 million cases of breast cancer were reported worldwide in 2018 [2]
The data indicate that crude extract prepared from the stem did not affect cell proliferation of HepG2 cells, and induced weak cytotoxicity in MDA and MCF7 cells
We showed that methanol extract of the shoots of M. sinaica induced G1 cell cycle arrest in MDA-MB-231 cells, as indicated by the increased proportion proportionofofcells cells phase compared with the control at at thethe compared with the control group
Summary
Breast cancer is a predominant cancer among women [1], and over 2 million cases of breast cancer were reported worldwide in 2018 [2]. The expression of hormone receptors is a predictive feature in breast cancer treatment. Estrogen and progesterone receptor-positive breast cancers have a more favorable prognosis and are more responsive to anti-estrogen therapy than that of estrogen and progesterone receptor-negative breast cancer [3]. Ten to twenty percent of breast cancer cases are triple-negative breast cancers (TNBC). TNBC grows more aggressively, and women diagnosed with TNBC typically have a higher mortality ratio [4]. There are very limited treatment options for TNBC, these mainly being chemotherapy and surgery, but the recurrence rate is higher compared to
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