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Grape Seed Extract Stops Head and Neck Cancers
Research Where Your Mouth Is: Grape Seed Extract and Oral Cancer
THE STUDY ABSTRACT:
THE STUDY ABSTRACT:
Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/ S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells.
Preventive measures against oral carcinogenesis are urgently warranted to lower the high morbidity and mortality associated with this malignancy worldwide. Here, we investigated the chemopreventive efficacy of grape seed extract (GSE) and resveratrol (Res) in 4-nitroquinoline-1-oxide (4NQO)-induced tongue tumorigenesis in C57BL/6 mice. Following 8 weeks of 4NQO exposure (100 µg/ml in drinking water), mice were fed with either control AIN-76A diet or diet containing 0.2% GSE (w/w) or 0.25% Res (w/w) for 8 subsequent weeks, while continued on 4NQO. Upon termination of the study at 16 weeks, tongue tissues were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for molecular targets by immunohistochemistry. GSE and Res feeding for 8 weeks, moderately decreased the incidence, but significantly prevented the multiplicity and severity of 4NQO-induced preneoplastic and neoplastic lesions, without any apparent toxicity. In tongue tissues, both 4NQO + GSE and 4NQO + Res treatment correlated with a decreased proliferation (BrdU labeling index) but increased apoptotic death (TUNEL-positive cells) as compared to the 4NQO group. Furthermore, tongue tissues from both the 4NQO + GSE and 4NQO + Res groups showed an increase in activated metabolic regulator phospho-AMPK (Thr172) and decreased autophagy flux marker p62. Together, these findings suggest that GSE and Res could effectively prevent 4NQO-induced oral tumorigenesis through modulating AMPK activation, and thereby, inhibiting proliferation and inducing apoptosis and autophagy, as mechanisms of their efficacy.
Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells.
Source: Shrotriya S, Deep G, Lopert P, Patel M, Agarwal R, Agarwal C. Mol Carcinog. 2015 Dec;54(12):1734-47.
WHAT IT MEANS TO YOU:
Normally, we think of any kind of oxidative damage as a bad thing, but this isn’t always the case. This study showed that grape seed extract actually induced oxidative damage in cancer cells. It interfered with the ability of the mitochondria—the “engine” of the cell—in this case, cancer cells—to thrive and create more cancer cells. This study shows one of the more surprising facets of grape seed extract—that an ingredient that can provide antioxidant defense for healthy, normal cells can have the opposite, targeted effect on tumors. Head and neck cancers remain a common cause of tumors, affecting more than 60,000 individuals annually. The research with grape seed extract could lead to life-saving interventions in the near future. 64
LIFESTYLES
Grape seed extract and resveratrol prevent 4-nitroquinoline 1-oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses.
Source: Shrotriya S, Tyagi A, Deep G, Orlicky DJ, Wisell J, Wang XJ, Sclafani RA, Agarwal R, Agarwal C. Mol Carcinog. 2015 Apr;54(4):291-300.
WHAT IT MEANS TO YOU:
Grape seed extract and resveratrol (found in red wine and grape seed extract) have been shown to work in tandem to control the spread of oral cancer tumors. Not only did this combination prevent oral cancer tumors from multiplying, it also lead to cancer cell death. These ingredients could inhibit pre-cancerous lesions from spreading or becoming potentially lethal tumors. The fact that both are fairly common supplemental ingredients means that stopping cancer—in some cases before it even starts—is within reach for almost everyone.