Synergistic interactions between black tea theaflavins and chemotherapeutics in oral cancer cells

Tehilla Raviv, Department of Biology, Stern College for Women, Yeshiva University, New York Alla Digilova, Department of Biology, Stern College for Women, Yeshiva University, New York Alyssa Schuck, Department of Biology, Stern College for Women, Yeshiva University, New York

Abstract Chemotherapeutic drugs are typically used for the treatment of cancer. However, chemotherapeutics often impose serious and debilitating side effects, such as nausea, fatigue, low white and red blood count, and hair loss, which detrimentally affect the patient’s quality of life. Therefore, supplementary methods to increase the efficacy of a chemotherapeutic, thereby allowing for lower patient dosages, would enhance both the drug treatment protocol and the patient’s quality of life. This research evaluated synergistic toxicity interactions between the chemotherapeutic, cisplatin (cis-diamminedichloridoplatinum(II)), and black tea theaflavins towards cancer cells in vitro. As the oral cavity is the site that initially contacts the black tea beverage and therefore is exposed to the highest concentration of theaflavins, cancer cells derived from tissues of the human oral cavity were utilized for this study. Black tea, one of the most widely consumed beverages worldwide, has received a great deal of attention from the scientific community due to its positive health effects, including the inhibition of tumorigenesis. Black tea contains several types of polyphenolic compounds that contribute to its anticarcinogenic effects, the most potent of which are the theaflavins. The theaflavins in black tea include theaflavin (TF-1), theaflavin-3-monogallate (TF-2A), theaflavin-3’-monogallate (TF-2B), and theaflavin-3,3’-digallate (TF-3). Previous studies demonstrated that a natural mixture of the four theaflavins exhibited pronounced growth-inhibitory effects on oral squamous carcinoma cells. However, gingival fibroblasts derived from normal tissue were less susceptible to the cytotoxic effects of the theaflavins. Experiments showed that this theaflavin mixture generated hydrogen peroxide, which accounted for the greater sensitivity of the cancer cells, since they already have compromised intracellular antioxidant defenses. The prooxidant activity of specific theaflavins were now investigated as a possible adjuvant to potentiate the potency of cisplatin towards cancer cells. In the present study, the relative cytotoxicities of the four theaflavins to oral squamous carcinoma cells were assessed with the neutral red assay. This assay is a cell-survival colorimetric assay based on the ability of viable cells to incorporate and bind the supravital dye, neutral red. The four theaflavins were cytotoxic to varying degrees, with TF-3 having the greatest cytotoxic activity. Additionally, TF-3 produced the highest levels of reactive oxygen species (ROS), and induced apoptotic cell death in carcinoma, but not in normal, cells. Cisplatin is a platinum-based chemotherapeutic, was chosen for this study because it is used for treatment of head and neck cancers and one of its modes of toxicity is the production of ROS. A combinatorial treatment of the cultured oral carcinoma cells with black tea theaflavins and cisplatin was performed. Based on the cytotoxicity assays, the black tea theaflavins were shown to synergize the potency of cisplatin. While in vivo studies are necessary, our data propose the possibility of administering lower dosages of cisplatin in conjunction with black tea. This combination therapy for the treatment of oral carcinoma patients could potentially reduce the risk of adverse side effects caused by chemotherapeutics.

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