Pro-apoptotic activity against cancer stem cells differs between different parts of sweet sorghum. (May 2016)

• Record Type: Journal Article
• Authors: Massey, Aaron R.; Reddivari, Lavanya; Radhakrishnan, Sridhar; Charepalli, Venkata; Kurundu Hewage, Eranda Karunathilake; Ramakrishna, Vadde; Vanamala, Jairam K.P.
• Is Part Of: Journal of functional foods. Volume 23(2016)
• Page Start: 601
• Page End: 613
• Publication Date: 2016-05
• Subjects: Sorghum bicolor -- Sweet sorghum -- Biorefinery -- Apoptosis -- Colon cancer stem cell; CCSC Human colon cancer stem cells -- PARP Poly ADP ribose polymerase -- BrdU Bromodeoxyuridine -- TUNEL Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labelling -- Wnt Wingless/integrated -- 5FU 5-Fluorouracil -- GSK-3β Glycogen synthase kinase isoform 3β -- ABTS 2, 2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) -- TPC Total phenolic content -- AOA Antioxidant activity -- DAP Days after planting -- TE Trolox equivalents; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2016.03.004
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Sweet sorghum (SS) is a rich source of bioactive 3-deoxyanthocyanidins. Dermal and seed head (SH) phenolics were most potent apoptotic agents. Dermal and SH induced apoptosis were p53-dependent and partially p53-dependent, respectively. SS bioactives targeted Wnt/β-catenin signalling pathway proteins. Abstract: The extracts from sweet sorghum stalk were previously shown to eliminate human colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms remain unknown. In this study, we transfected CCSC with shRNA against p53 and treated with sweet sorghum phenolics extracted from different plant components. While all sweet sorghum components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspase 3/7 activity, poly ADP-ribose polymerase cleavage, and DNA fragmentation in a p53-dependent and partial p53-dependent manner, respectively. These effects were associated with decreases in β-catenin, cyclin D1, cMyc, and survivin protein levels. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against CCSC are potentially via suppression of Wnt/β-catenin signalling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner.