α-Mangostin and Apigenin Induced Cell Cycle Arrest and Programmed Cell Death in SKOV-3 Ovarian Cancer Cells

• Published in: Toxicological research (Seoul) Vol. 35; no. 2; pp. 167 - 179
• Main Authors: Ittiudomrak, Teeranai, Puthong, Songchan, Roytrakul, Sittiruk, Chanchao, Chanpen
• Format: Journal Article
• Language: English
• Published: Singapore 한국독성학회 01.04.2019; Springer Singapore; Korean Society of Toxicology
• Subjects: Biomedicine; Original; Original Article; Pharmacology/Toxicology; 예방의학; Cell cycle arrest; Caspase activity; Apigenin; α-Mangostin; Apoptosis; Ovarian cancer
• ISSN: 1976-8257; 2234-2753
• DOI: 10.5487/TR.2019.35.2.167

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, α-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. α-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 α-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas α-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in α-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 α-mangostin and apigenin arrested the cell cycle at the G 2 /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 α-mangostin-treated SKOV-3 cells, respectively. α-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 α-mangostin likely being involved with inflammation.