Jin-Sik Nam1,2,3, Seo-Yeon Park2, Seon-Ok Lee4, Hyo-Jeong Lee4, Hye-Lim Jang5, Young Ha Rhee6. 1. Department of Food and Nutrition, Suwon Women's University, 1098 Juseok-ro, Bongdam-eup, Hwaseong-si, Gyeonggi, 18333, Republic of Korea. 2. Food Analysis Research Center, Suwon Women's University, 1098 Juseok-ro, Bongdam-eup, Hwaseong-si, Gyeonggi, 18333, Republic of Korea. 3. Department of Microbiology and Molecular Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea. 4. College of Korean Medicine and Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. 5. Department of Food and Nutrition, Dong-eui University, 176 Eomgwang-ro, Busanjin-gu, Busan, 47340, Republic of Korea. forest2852@deu.ac.kr. 6. Department of Microbiology and Molecular Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea. yhrhee@cnu.ac.kr.
Abstract
BACKGROUND: The pawpaw tree has several beneficial effects. However, no studies have been conducted to address the mechanisms underlying the cytotoxic effects of pawpaw extracts against cancer cells, and no study has investigated the anti-inflammatory effects. Hence, in this study, the growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) extracts against gastric (AGS) and cervical (HeLa) cancer cells and the inhibitory effects of pawpaw extracts against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated. METHODS AND RESULTS: The viability of AGS and HeLa cells, the analysis of cell cycle, and the expression of apoptosis marker protein were determined using MTT assay, FACS, western blotting, and TUNEL assays. The inflammatory factors were determined using Griess method, ELISA assay kit, and RAW 264.7 cells. The IC50 values of twig and unripe fruit extracts for AGS cells were 82.01 and 100.61 µg/mL, respectively. For HeLa cells, pawpaw twig extracts exhibited the strongest ability to inhibit cervical cancer cell growth (IC50 = 97.73 µg/mL). Analysis of the cell cycle phase distribution and expression of the apoptosis regulatory proteins BCL-2, BAX, caspase-3, and PARP showed that pawpaw twig, root, and unripe fruit extracts induced Sub G1 cell cycle arrest and apoptosis of AGS and HeLa cells. In addition, the twig, root, and unripe fruit extracts of pawpaw effectively inhibited the inflammatory makers NO, TNF-α, IL-6, and iNOS. Particularly, the twig, root, and unripe fruit extracts at concentrations of 50 µg/mL exhibited > 50% inhibition of TNF-α. CONCLUSIONS: These findings indicate that pawpaw extracts are natural therapeutic agents that may be used for the prevention and treatment of gastric and cervical cancers, and encourage further studies on the anti-inflammatory potential of the pawpaw tree.
BACKGROUND: The pawpaw tree has several beneficial effects. However, no studies have been conducted to address the mechanisms underlying the cytotoxic effects of pawpaw extracts against cancer cells, and no study has investigated the anti-inflammatory effects. Hence, in this study, the growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) extracts against gastric (AGS) and cervical (HeLa) cancer cells and the inhibitory effects of pawpaw extracts against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated. METHODS AND RESULTS: The viability of AGS and HeLa cells, the analysis of cell cycle, and the expression of apoptosis marker protein were determined using MTT assay, FACS, western blotting, and TUNEL assays. The inflammatory factors were determined using Griess method, ELISA assay kit, and RAW 264.7 cells. The IC50 values of twig and unripe fruit extracts for AGS cells were 82.01 and 100.61 µg/mL, respectively. For HeLa cells, pawpaw twig extracts exhibited the strongest ability to inhibit cervical cancer cell growth (IC50 = 97.73 µg/mL). Analysis of the cell cycle phase distribution and expression of the apoptosis regulatory proteins BCL-2, BAX, caspase-3, and PARP showed that pawpaw twig, root, and unripe fruit extracts induced Sub G1 cell cycle arrest and apoptosis of AGS and HeLa cells. In addition, the twig, root, and unripe fruit extracts of pawpaw effectively inhibited the inflammatory makers NO, TNF-α, IL-6, and iNOS. Particularly, the twig, root, and unripe fruit extracts at concentrations of 50 µg/mL exhibited > 50% inhibition of TNF-α. CONCLUSIONS: These findings indicate that pawpaw extracts are natural therapeutic agents that may be used for the prevention and treatment of gastric and cervical cancers, and encourage further studies on the anti-inflammatory potential of the pawpaw tree.
Authors: H C Reinecker; M Steffen; T Witthoeft; I Pflueger; S Schreiber; R P MacDermott; A Raedler Journal: Clin Exp Immunol Date: 1993-10 Impact factor: 4.330