Cytotoxic activity of phytochemicals from Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly against breast cancer cells

Abstract

Four xanthones, α-mangostin (1), β-mangostin (2), mangostenol (3), mangaxanthone B (4), three benzophenones, mangaphenone (5), benthamianone (6), congestiflorone (7) and one sterol, stigmasterol (8) were isolated from the stem barks of Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly. Compounds 1, 2, 4 and 5 exhibited significant cytotoxicity through MTT assay towards MCF-7 and MDA-MB-231 cells with the IC₅₀ values range from 4.4 to 12.0 µM. Remarkably, mangaphenone (5) showed non-cytotoxicity against normal Vero cells, revealing its potential as lead compound for anti-breast cancer drug. Structure–activity relationship postulated that the prenyl and hydroxyl groups present in xanthones are important in promoting anti-proliferative effects. Molecular docking simulation study of 1, 2, 4 and 5 with 2OCF and 4PIV implied that the induction of apoptosis for both cancer cells involve ER and FAS signaling pathways. Future study on the lead optimization of 5 is highly recommended.

Graphical Abstract

Keywords:

• Benzophenone
• MCF-7
• MDA-MB-231
• molecular docking
• structure–activity relationship
• xanthone

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like to acknowledge financial support from the Malaysian Ministry of Education (MOE) under the Fundamental Research Grant Scheme (FRGS/1/2019/STG01/TAYLOR/02/1). The Sarawak Biodiversity Centre (SBC) is also acknowledged.