Promising Compounds From Murraya exotica for Cancer Metastasis Chemoprevention

Abstract

Most of the present anticancer drugs are highly cytotoxic and focus mainly on killing tumor cells rather than slowing the progress of cancer metastasis. Evidence has been reported that bridges the mechanisms of inflammation and tumor invasion. Therefore, we evaluated the potency in cancer metastasis chemoprevention of compounds and a coumarin extracted from Murraya exotica, which is known for its anti-inflammation bioactivity. By carrying out experiments in vitro, we found the root extracts more efficient than the leaf extracts in restraining cell migration of MDA-MB-231 cells, while leaf extracts presented slightly stronger inhibition of tumor cell adhesion at low concentrations. In addition, compared to root extracts, a novel coumarin identified previously from root extracts showed equal inhibition on cancer cell adhesion and less inhibition on cell migration. All extracts used in this study presented low cytotoxicity in vitro. Through comparison of the contents of leaf and root extracts from M exotica, several compounds are considered promising against cancer metastasis. This study evaluates the worth of further development of M exotica to find its effect on cancer metastasis chemoprevention.

Keywords: Murraya exotica; cancer metastasis chemoprevention; cell adhesion; cell migration; coumarin.

Figure 1.

Structure of identified compounds. (A) Structure of murrayone (7-methoxy-8-(3-methyl-2-oxobut-3-enyl)chromen-2-one) (retention time at 7.87 minutes in leaf extracts). (B) Structure of 7-methoxy-8-(2′-methyl-2′-formylpropyl)-coumarin (retention time at 4.57 minutes in leaf extracts). (C) Structure of trihydroxy coumarin (retention time at 8.98 minutes in leaf extracts). (D) Structure of 5,7-dimethoxy-8-(3-methyl-2-keto-butyl) coumarin (retention time at 9.08 minutes in root extracts). (E) The elucidated chemical structure 7-methoxy-8-(5-(prop-1-en-2-yloxy)penta-1,3-dien-1-yl)-coumarin (CM1, retention time at 1.89 minutes in root extracts), labeling with the assignment of H atoms.

Figure 2.

HPLC result of CM1. CM1 at retention time of 5 minutes is purified by a semipreparative HPLC procedure. Purification is further confirmed by UV detection.

Figure 3.

Bioactivity of CM1, root extracts, and leaf extracts. (A) MTT test results of MDA-MB-231 cells under the treatment of CM1, leaf extract, and root extract. (B) Static adhesion test between MDA-MB-231 cells and HPMEC cells under the treatment of CM1, leaf extract, and root extract. (C) Wound healing assay results of MDA-MB-231 cells under the treatment of CM1, leaf extract, and root extract. (D) Sample photographs of CM1 group, leaf group, and root group at 50 µg/mL in comparison with control group in the scratch assay. (E) Sample photographs of CM1 group, leaf group, and root group at 50 µg/mL in comparison with control group in the adhesion assay. Single asterisk stands for significant difference with P < .05. Double asterisks stand for significant difference with P < .01.