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Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress

Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Korea
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Biomolecules 2020, 10(10), 1380; https://doi.org/10.3390/biom10101380
Received: 2 September 2020 / Revised: 23 September 2020 / Accepted: 27 September 2020 / Published: 28 September 2020
(This article belongs to the Special Issue Bioactive Formulations in Agri-Food-Pharma: Source and Applications)
Notably, 6-Shogaol, a bioactive natural substance, has anticancer effects on many types of tumors. Up to date, the anticancer effect and mode of action of 6-Shogaol on liposarcoma are not known. In this study, we investigated whether 6-Shogaol inhibits the growth of SW872 and 93T449 cells, two different human liposarcoma cell lines. Of note, 6-Shogaol inhibited the growth of SW872 and 93T449 cells without affecting that of normal 3T3-L1 preadipocytes. Specifically, 6-Shogaol further induced the apoptosis of SW872 cells, as evidenced by nuclear DNA fragmentation, increased sub G1 population, activation of the intrinsic caspase pathway, and PARP cleavage. However, pretreatment with either z-VAD-fmk, a pan-caspase inhibitor, or N-acetylcysteine, an antioxidant, attenuated the 6-Shogaol’s growth-suppressive and apoptosis-inducing effects on SW872 cells. Moreover, 6-Shogaol activated AMPK while inhibited STAT-3 in SW872 cells, and siRNA-based genetic silencing of AMPK or STAT-3 considerably blocked the growth-suppressive and apoptotic response of 6-Shogaol to SW872 cells. Moreover, 6-Shogaol also upregulated the expression and phosphorylation of GRP-78, eIF-2α, ATF4, and CHOP, known ER stress markers, in SW872 cells, illustrating the induction of ER stress. These findings collectively demonstrate that 6-Shogaol has strong antigrowth and proapoptotic effects on SW872 cells through regulation of the intrinsic caspase pathway, oxidative stress, STAT-3, AMPK, and ER stress. View Full-Text
Keywords: 6-shogaol; caspase-9; AMPK; STAT-3; ER stress; SW872 6-shogaol; caspase-9; AMPK; STAT-3; ER stress; SW872
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MDPI and ACS Style

Yadav, A.K.; Jang, B.-C. Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress. Biomolecules 2020, 10, 1380. https://doi.org/10.3390/biom10101380

AMA Style

Yadav AK, Jang B-C. Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress. Biomolecules. 2020; 10(10):1380. https://doi.org/10.3390/biom10101380

Chicago/Turabian Style

Yadav, Anil K.; Jang, Byeong-Churl. 2020. "Anti-Survival and Pro-Apoptotic Effects of 6-Shogaol on SW872 Human Liposarcoma Cells via Control of the Intrinsic Caspase Pathway, STAT-3, AMPK, and ER Stress" Biomolecules 10, no. 10: 1380. https://doi.org/10.3390/biom10101380

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