New xanthones and cytotoxic constituents from Garcinia mangostana fruit hulls against human hepatocellular, breast, and colorectal cancer cell lines

• Published in: Journal of ethnopharmacology 2017-02, Vol.198 (NA), p.302-312
• Main Authors: Mohamed, Gamal A., Al-Abd, Ahmed M., El-halawany, Ali M., Abdallah, Hossam M., Ibrahim, Sabrin R.M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; antiproliferative; Apoptosis - drug effects; benzophenones; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; cytotoxic activity; Female; Flow Cytometry; Fruit; Garcinia mangostana; Garcinia mangostana - chemistry; HCT116 Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; mangostanaxanthone; MCF-7 Cells; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - pharmacology; xanthones; Xanthones - administration & dosage; Xanthones - isolation & purification; Xanthones - pharmacology
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2017.01.030

Cancer has proceeded to surpass one of the most chronic illnesses to be the major cause of mortality in both the developing and developed world. Garcinia mangostana L. (mangosteen, family Guttiferae) known as the queen of fruits, is one of the most popular tropical fruits. It is cultivated in Southeast Asian countries: Malaysia, Indonesia, Sri Lanka, Burma, Thailand, and Philippines. Traditionally, numerous parts of G. mangostana have been utilized to treat various ailments such as abdominal pain, haemorrhoids, food allergies, arthritis, leucorrhoea, gonorrhea, diarrhea, dysentery, wound infection, suppuration, and chronic ulcer. Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated. The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry. The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additio