Open AccessCHEMICAL INVESTIGATION AND ANTIPROLIFERATIVE STUDIES OF ISOLATED POLYISOPRENYLATED BENZOPHENONES FROM STEM-BARK OF Garcinia maingayi
Author(s) -
Sangeetha Arullappan,
Wong Fai Chu,
Lim Chan Kiang,
Vivien Jong Yi Mian,
Sim Kooi Mow
Publication year - 2021
Publication title -
journal of experimental biology and agricultural sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.108
H-Index - 2
ISSN - 2320-8694
DOI - 10.18006/2021.9(spl-1-gcsgd_2020).s71.s84
Subject(s) - hela , apoptosis , chemistry , flow cytometry , cell cycle , mtt assay , cell cycle checkpoint , microbiology and biotechnology , caspase , annexin , cell culture , stereochemistry , cell , biochemistry , programmed cell death , biology , genetics
In the current study, sequential solvents extraction from the stem bark of Garcinia maingayi, a native plant to Malaysia has led to the isolation of four polyisoprenylated benzophenones: 30-epi-cambogin (GB 1), 14-deoxy-30-epi-cambogin (GB 2), guttiferone F (GB 3), and 14-deoxy-guttiferone F (GB 4). The structures were elucidated using IR, optical rotation, and NMR spectral data. The compounds were evaluated for antiproliferative effect using MTT assay, apoptosis using Annexin V/7-AAD flow cytometry, cell cycle progression, and activation of caspases 3/7, 8 and 9 and BCL2 mRNA expression in MCF-7, HeLa, and HepG2 cancer cell lines. Compounds GB 1 to GB 4 exhibited a remarkable antiproliferative effect on HeLa, MCF-7, and HepG2 cells with IC50 values ranging from 5 to 45 µM. Compounds GB 1 to GB 4 induced significant cell cycle arrest in the G1 phase corroborated with the decrease in the number of MCF-7 and HepG2 cells in S and G2/M phases (P<0.05). Compounds GB 1 to GB 4 induced apoptosis at 48 h. Further, among these, compounds GB 1 and GB 2 induced significant levels of caspases 3 and 9 in HeLa cells, while GB 3 induced caspase 9 activities in both MCF-7 and HepG2 cells. No significant induction of caspase 8 was observed suggesting that the apoptotic effects are mainly mediated through the intrinsic pathway. Only compound GB 1 inhibited the BCL2 mRNA expression significantly in all treated cancer cells. In conclusion, these compounds possess anticancer properties and thus further investigation is crucial on the mechanistic study, structure-activity relationship, and identification of putative molecular targets.