The safety and efficacy of Meriva (R) and ginger extract combination in Pheroid (R) against lung cancer

Abstract

Lung cancer is the leading cause of cancer related deaths, globally, with poor survival profile. Cisplatin is frequently used in the treatment of many solid tumors including lung cancer despite its toxicity; ototoxicity, peripheral neuropathy, and nephrotoxicity. Turmeric and ginger extracts constitute a mix of biologically active compounds such as curcumin and [6]-shogaol with established chemopreventive, anti-inflammatory and antioxidant properties. Human clinical safety data show that turmeric and ginger extracts exhibit low intrinsic toxicity even at higher doses. The present in vitro safety study investigated the chemopreventive activity of combined Meriva® (a curcumin phytosome) and ginger extract in Pheroid® delivery system against the A549 lung cancer cell line. Pheroid® is a colloidal emulsion system comprised of plant and ethyl esters of essential fatty acids (EFAs) as the dispersed phase and nitrous oxide saturated water as the continuous phase. Six combinations of Meriva® and ginger extract were formulated in Pheroid®. The contents of curcumin in Meriva® and [6]-shogaol in ginger extract were quantified using LC-MS/MS. Cell viability was studied using MTT and neutral red uptake assays. Cellular uptake as well as safety in terms of induction of oxidative stress markers including reactive oxygen species (ROS), superoxide dismutase (SOD) and catalase (CAT) were examined between Pheroid® formulated phytochemical combination and cisplatin. Pheroid® enhanced cellular uptake of Meriva® and ginger extract combination and proved to be safe despite higher concentration of the actives were present in the cells. Meriva® and ginger extract at 1:1.43 combination ratios in Pheroid® had a comparable anticancer activity with cisplatin. In the oxidative stress test, cisplatin induced significantly higher ROS and lower CAT levels, and insignificantly lowered SOD level compared to the control while the same Meriva® and ginger extract combination in Pheroid® showed insignificantly lower ROS level and significantly lower SOD and CAT levels compared to the control. The content of curcumin in Meriva® and [6]-shogaol in ginger extract were found to be 400 mg/g and 10.61 mg/g, respectively. Although cisplatin is an effective antineoplastic agent, its side effects stem from its nonselective induction of oxidative stress to both cancer and normal cells. Pheroid® formulated Meriva® and ginger extract combination demonstrated a comparable anticancer activity with cisplatin without induction of oxidative stress and can therefore be used as a safe and effective adjuvant therapy in lung cancer