Despite their different effects on cell survival the functio

Despite their different effects on cell survival, the functions of autophagy and apoptosis are not completely independent. Additionally, Cho et al. (2009) suggested that the mediation of caspase-3 links the apoptotic and autophagic signaling pathways. Consequently, to illuminate the correlation, excess iodine was used in combination with the autophagy inhibitor 3-MA and the autophagy inducer rapamycin to measure the expression level of the apoptosis-associated protein cleaved-caspase-3 in SH-SY5Y cells. As expected, our results showed that 3-MA and high iodide significantly enhanced the expression levels of the apoptosis protein cleaved-caspase-3, the data implied that autophagy is involved in high iodide-induced apoptosis in SH-SY5Y cells. Additionally, rapamycin administration strongly reduced caspase-3 activation, indicating that autophagy and apoptosis, of which caspase-3 activation is considered a hallmark, are tightly correlated phenomena. Previous studies have demonstrated that the inhibition of autophagy triggers apoptotic cell death (Boya et al., 2005, Gonzalez-Polo et al., 2007). Furthermore, rapamycin-induced autophagy prevents apoptosis (Park et al., 2013). Consistent with these previous studies, our results indicate the possibility that autophagy may regulate apoptotic cell death induced by high iodide in SH-SY5Y cells. In addition, research has shown that the administration of rapamycin increases autophagy and significantly reduces MK 571 sale damage (Carloni et al., 2010). In our study, enhancement of autophagy by rapamycin reduced the level of apoptosis. It is very likely that autophagy has a protective effect against high iodide-induced apoptosis in which autophagy and apoptosis interplay. More research would be needed to study the complex mechanisms underlying the interplay between autophagy and apoptosis induced by high levels of iodide.
Conflict of interest statement
Acknowledgements This work was supported by the National Natural Science Foundation of China [grant numbers 81372934, 81573107, and 81430076] and Scientific and Technological Project of Tianjin Medicine in 2014 [grant number 14KG120].
Introduction Colorectal cancer, also known as bowel or colon cancer, is one of the most prevalent and leading causes of cancer-related morbidity and mortality worldwide next to lung cancer [1], [2]. Factors such as bad dietary habits, smoking status, alcohol consumption, genetic predisposition, diabetes and sedentary lifestyle significantly increase the risk of developing colorectal cancer [3], [4]. To date, standard treatment for colorectal cancer includes surgery, such as right colectomy, sigmoid colectomy and total abdominal colectomy with ileorectal anastomosis as well as chemotherapy [3], [5]. Early polyps detection can often leads to a complete cure among patients; however, in most cases the polyps go undetected leading to increased risk of mortality. In such cases, patients with advanced stage of colorectal cancer are normally treated with chemotherapeutic drug, 5-fluorouracil (5-FU) alone or in combination of adjuvant such as oxaliplatin and avastin [6], [7]. Even though such treatment modalities improve disease and overall survival, nonetheless, the use of chemotherapeutic drugs induces severe toxicity and lethality on normal cells with side-effects, such as severe nausea, vomiting, weight loss and risk of infectious complications due to immunosuppression that often burden the patients [8], [9]. In the last decade, the research trend has focused on the application of alternative and complementary medicines, specially functional foods, through the potentiation of nutraceuticals for the treatment and prevention of various diseases, such as inflammation, cancer, immunity, diabetic, bacterial & viral infections and antiaging agents due to their capability to evoke various signaling pathways, nutritional values with no or marginal side-effects and toxicity [10], [11], [12], [13], [14], [15], [16]. More importantly, various bioactive compounds have been used in pre-clinical and clinical studies since they are capable to activate various signaling machineries in promoting tumor elimination such as cell cycle arrestment, antiangiogenesis, enhancement of immune response, induction of apoptosis and DNA damage with marginal side-effects [17], [18], [19], [20]. Prophetic medicines comprising of dietary materials usage or remedy recipes from plants or herbals that were used by the Prophet Mohammed (PBUH) are among the alternative and complementary medicines that hold future therapeutic promise against chronic diseases [21]. Plants or herbals or dietary functional foods or spices, such as Cymbopogon citratus, Nigella sativa, olives and ginger are rich in bioactive compounds such as shogaol and thymoquinone that possess potent antitumor, antiangiogenic, antiproliferative and antimetastatic activities with minimal side-effects and low toxicity level [10], [22], [23]. C. citratus or lemongrass, a Prophetic medicine, is spontaneous perennial grass that is widely used as herb in cooking or as a source of ethnomedicine to treat various ailments such as diabetes, digestive disorders, fever and inflammation [24], [25]. The 80%-ethanol extract of C. citratus (at 0.5 or 5g/kg) suppressed azoxymethane (AOM)-induced rat colon carcinogenesis model by inhibiting the DNA adduct formation in both the colonic mucosa and the muscular layer and the formation of aberrant crypt foci (ACF formation) in both the initiation stage and the promotion stage (larger ACF with four or more crypts per focus) [26]. In a more recent finding, the C. citratus essential oil (500mg/kg) significantly protected the female Balb/C mice against MNU-induced DNA damage and DDB-induced mammary carcinogenesis (alveolar and ductal mammary hyperplasia) [27].