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Open AccessArticle

Proanthocyanidin-Rich Fractions from Red Rice Extract Enhance TNF-α-Induced Cell Death and Suppress Invasion of Human Lung Adenocarcinoma Cell A549

1
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2
Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3
Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai 50200, Thailand
*
Author to whom correspondence should be addressed.
Academic Editor: Roberto Fabiani
Molecules 2019, 24(18), 3393; https://doi.org/10.3390/molecules24183393
Received: 23 August 2019 / Revised: 10 September 2019 / Accepted: 17 September 2019 / Published: 18 September 2019
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
Tumor necrosis factor-alpha (TNF-α) plays a key role in promoting tumor progression, such as stimulation of cell proliferation and metastasis via activation of NF-κB and AP-1. The proanthocyanidin-rich fraction obtained from red rice (PRFR) has been reported for its anti-tumor effects in cancer cells. This study investigated the molecular mechanisms associated with PRFR on cell survival and metastasis of TNF-α-induced A549 human lung adenocarcinoma. Notably, PRFR enhanced TNF-α-induced A549 cell death when compared with PRFP alone and caused a G0-G1 cell cycle arrest. Although, PRFR alone enhanced cell apoptosis, the combination treatment induced the cells that had been enhanced with PRFR and TNF-α to apoptosis that was less than PRFR alone and displayed a partial effect on caspase-8 activation and PARP cleavage. By using the autophagy inhibitor; 3-MA attenuated the effect of how PRFR enhanced TNF-α-induced cell death. This indicates that PRFR not only enhanced TNF-α-induced A549 cell death by apoptotic pathway, but also by induction autophagy. Moreover, PRFR also inhibited TNF-α-induced A549 cell invasion. This effect was associated with PRFR suppressed the TNF-α-induced level of expression for survival, proliferation, and invasive proteins. This was due to reduce of MAPKs, Akt, NF-κB, and AP-1 activation. Taken together, our results suggest that TNF-α-induced A549 cell survival and invasion are attenuated by PRFR through the suppression of the MAPKs, Akt, AP-1, and NF-κB signaling pathways. View Full-Text
Keywords: proanthocyanins; TNF-α; autophagy; invasion; lung adenocarcinoma proanthocyanins; TNF-α; autophagy; invasion; lung adenocarcinoma
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MDPI and ACS Style

Subkamkaew, C.; Limtrakul (Dejkriengkraikul), P.; Yodkeeree, S. Proanthocyanidin-Rich Fractions from Red Rice Extract Enhance TNF-α-Induced Cell Death and Suppress Invasion of Human Lung Adenocarcinoma Cell A549. Molecules 2019, 24, 3393.

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