%0 Journal Article
%T ¦Á-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells
%A Chanpen Chanchao
%A Sittiruk Roytrakul
%A Songchan Puthong
%A Teeranai Ittiudomrak
%J Archive of "Toxicological Research".
%D 2019
%R 10.5487/TR.2019.35.2.167
%X Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ¦Á-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ¦Á-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ¦Á-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ¦Á-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ¦Á-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ¦Á-mangostin and apigenin arrested the cell cycle at the G2/M phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ¦Á-mangostin-treated SKOV-3 cells, respectively. ¦Á-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ¦Á-mangostin likely being involved with inflammation
%K ¦Á-Mangostin
%K Apigenin
%K Apoptosis
%K Caspase activity
%K Cell cycle arrest
%K Ovarian cancer
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467359/