The leading causes of oral cancer treatment failure are cancer metastasis and chemotherapeutic resistance. Thus, developing novel anticancer agents that are effective against those aggressive cancer cells would be important for complementary or alternative treatments. The objective of this study was to investigate cytotoxicity and anticancer mechanisms of a synthetic trienone analog of curcumin, 1,7-bis(3-hydroxyphenyl)-1,4,6-heptatrien-3-one (trienone 11), against human oral squamous cell carcinoma (OSCC) cells exhibiting multidrug resistance (CLS-354/DX). The study of cytotoxicity showed that trienone 11 exerted threefold stronger cytotoxicity to CLS-354/DX cells than curcumin. Trienone 11 (15-30 μM) markedly induced intracellular reactive oxygen species (ROS) resulting in apoptotic cell death within 24 h, through activation of caspase-3/7 and caspase-9. A ROS inhibitor, N-acetylcysteine (NAC) prevented apoptotic cell death via decreasing caspase activation. Thus, the cytotoxicity of trienone 11 against CLS-354/DX cells was ROS-mediated intrinsic apoptosis. Overall, trienone 11 could be an interesting lead for developing anti-cancer agents against multidrug resistant OSCC cells.

Radicals derived from exogenous and endogenous sources are considered to be the principal cause of genetic damage. Exogenous and endogenous radicals participate in the reactive oxygen species (ROS) formation, which leads to damages in the DNA, RNA, proteins and lipids. However, dietary compounds, mainly from pigmented rice, are an essential source of antioxidants that help protect cells from damage. This study seeks to determine the antioxidant properties and cytoprotective effect of two Thai pigmented rice extracts namely the glutinous black rice (native name: Neaw dum moa37) and red rice (native name: Hom gradung-nga57) on H2O2-induced damage in HT-29 cells. The bioactive compound contents, as well as antioxidant activities of both rice extracts, were investigated. The protective effect of rice extracts on H2O2-induced damage was executed following the co-incubation method. HT-29 cells were exposed to H2O2 and different rice extract concentrations for 3 h and an MTT assay was used to measure the viability of the cell. The ROS level was determined using the 2′,7′-dichlorofluorescin diacetate (DCFDA). The result showed that glutinous black rice extract contained significantly higher contents of all analysed antioxidants and activities than red rice extract. Glutinous black rice showed a higher cytotoxic effect compared to red rice. At the non-toxic concentration of both rice extracts, the HT-29 cells were guarded against the H2O2 induced oxidative stress. Besides, the intracellular ROS accumulation result from H2O2 exposure was significantly reduced in the presence of rice extracts for both glutinous black rice and red rice compared to control. Hence, this study has demonstrated the potential properties of both pigmented rice extracts in alleviating H2O2-mediated damage in HT-29 cells.

Pigmented rice is considered as the good source of phytochemicals which contains more phenolic contents and higher antioxidant activities compared with non-pigmented rice. However, those phytochemicals are normally extracted using inorganic solvent, using water was rarely found. This study was aimed to compare extraction methods on antioxidant contents and activities of two types of Thai pigmented rice (black glutinous rice and red non-glutinous rice). Pigmented rice was extracted either conventional method alone or a combination of ultrasonic plus conventional method with different solvents (methanol and hot water). Phenolic contents were analyzed by spectrophotometric assay and high-performance liquid chromatography (HPLC). Antioxidant activities were investigated by radical scavenging capacity (ABTS and DPPH). The results showed that ultrasonic pretreatment significantly enhanced the total phenolic, flavonoid, anthocyanin contents and higher antioxidant activities compared with conventional extraction irrespective of solvents and rice varieties. Ultrasonic methanol (UM) extraction proved to extract significant higher content of all the compounds analyzed in both the rice varieties. In contrast, hot water (HW) extracts exhibited the lowest amount of bioactive compounds. However, there was no significant difference between methanol extraction alone and ultrasonic pretreatment with hot water extract on antioxidant contents for black glutinous rice. The contents of individual anthocyanins and flavonoids (cyanidin 3-O-glucoside, peonidin 3-O-glucoside, and quercetin) were significantly increased with ultrasonic pretreatment compare to the conventional method in black glutinous rice while failed to detect the red rice variety. The black glutinous rice contained significantly higher contents of all analyzed compounds and antioxidant activities than red rice. In conclusions, our results demonstrated that ultrasonic pretreatment significantly enhanced antioxidant extraction with higher activities compared with conventional extraction irrespective of solvents and rice varieties. Furthermore, the efficiency of ultrasonic together with hot water extraction was almost equal to methanol extraction which was the one effective solvent for extracting antioxidant.