7-Geranyloxycinnamic Acid Isolated from Melicope lunu-ankenda Leaves Perturbs Colon Cancer and Breast Cancer Cell Lines’ Growth via Induction of Apoptotic Pathway

Abstract

Globally, breast cancer is the most prevalent form of cancer in women and there is a need for alternative therapies such as plant-derived compounds with low systemic toxicity and selective toxicity to cancer cells. The aim of this study is to assess the cytotoxicity effects of 7-geranyloxycinnamic acid isolated from leaves of Melicope lunu-ankenda, a traditional medicinal plant, on the human breast cancer cell lines. Dried leaf powder was used for the preparation of different crude extracts using different solvents of increasing order of polarity. The structure of the isolated compound from the petroleum ether extract was elucidated by 1H and 13C NMR, LC-MS, and DIP−MS spectroscopy. The cytotoxic activity of the crude extract and 7-geranyloxycinnamic acid analyzed using MTT assay. Apoptotic analysis was evaluated using Annexin V-PI staining, AO/PI staining, intracellular ROS measurement, and measurement of activities of caspases 3/7, 8, and 9. Crude extracts and the isolated pure compound showed significant cytotoxicity against tested cancer cell lines. 7-geranyloxycinnamic acid was found to exert significant cytotoxic effects against breast cancer cell lines such as the MCF-7 and MDA-MB-231 cell lines. The cytotoxic effects are attributed to its ability to induce apoptosis via accumulation of ROS and activation of caspases in both breast cancer cell lines. The pure compound, 7-geranyloxycinnamic acid isolated from the leaves of M. lunu-ankenda, can exert significant cytotoxic effects against breast cancer cell lines without affecting the normal cells.

A Review of the Ethnomedicinal, Phytochemical, and Anticancer Properties of Melicope Species

“…[39] It was also reported that the compound possessed the ability to induce apoptosis through the accumulation of ROS and activation of caspases in the breast cancer cell lines. [39]…”

“…In a recent study, 7‐geranyloxycinnamic acid was isolated from the leaves of M. lunu‐ankenda which showed selective cytotoxicity against breast cancer cell lines namely MCF‐7 and MDA‐MB‐231 at IC 50 of 4.936±0.345 and 5.368±0.777 μg/mL respectively [39] . It was also reported that the compound possessed the ability to induce apoptosis through the accumulation of ROS and activation of caspases in the breast cancer cell lines [39] …”

“…They are O-methyloktadrenolon, alloevodionol, isopimpinellin, alloxanthoxyletin, methylevodionol, and N-methylflindersine. [43] The isolation and extraction work on dry leaves of methanol extract had successfully characterized five spiroke- [39] In another study, the isolation and extraction of M. latifolia successfully isolated two monoterpenoids and four coumarins. The monoterpenoids are melifoliones A and melifoliones B while the four coumarin derivatives are bergapten, 5,7,8trimethoxycoumarin, 6,7,8-trimethoxycoumarin, and bruceol.…”

“…The spiroketals are melicospiroketal A, melicospiroketal B, melicospiroketal C, melicospiroketal D, melicospiroketal E. The phloroacetophenone and benzopyrans are 5‐C‐β‐ D ‐glucopyranosyl‐3‐C‐(6‐O‐trans‐p‐coumaroyl)‐β‐ D ‐glucopyranoside phloroacetophenone, 7‐acetyl‐6‐hydroxy‐5,8‐dimethoxy‐2,2‐dimethyl‐2H‐1‐benzopyran and 6‐acetyl‐8‐hydroxy‐5,7‐dimethoxy‐2,2‐dimethyl‐2H‐1‐benzopyran, respectively. Meanwhile another 16 compounds are 3,5‐di‐C‐β‐ D ‐glucopyranosyl phloroacetophenone, kaempferol 3‐robinobioside, kaempferol 3‐O‐β‐ D ‐glucopyranosyl‐α‐ D ‐xylopyranoside, icariside B 5 , tamarixetin 3‐robinobioside, leptonol, 8‐acetyl‐7‐hydroxy‐5,6‐dimethoxy‐2,2‐dimethyl‐2H‐l‐benzopyran, evodione, leptene A, isoevodionol, 6‐acetyl‐7‐hydroxy‐5‐methoxy‐2,2‐dimethyl‐2H‐chromene, 6‐(1‐methoxyethyl)‐5,7,8‐trimethoxy‐2,2‐dimethyl‐2H‐l‐benzopyran, acronyculatin G, 6‐(l‐hydroxyethyl)‐5,7,8‐trimethoxy‐2,2‐dimethyl‐2H‐1‐benzopyran, 3,5,4’‐trihydroxy‐8,3’‐dimethoxy‐7‐(3‐methyl but‐2‐enyloxy)flavone and 3,5,30‐trihydroxy‐8,40‐dimethoxy‐7‐(3‐methyl but‐2‐enyloxy) flavone [39] …”