Autophagy is a degradative process involving sequestration of cytoplasm and organelles into double-membrane vesicles that traffic the contents to lysosomes where recycling takes place [
1‐
3]. It is a genetically programmed, evolutionarily conserved process, typically observed in hepatocytes after amino acid deprivation [
4]. Recently, extensive attention has been paid to the role of autophagy in cancer development and therapy [
5‐
8]. There is increasing evidence suggesting that radiation and chemotherapeutic agents induce autophagy in many human cancer cell lines [
9‐
11]. In some cases, autophagy is one of the defensive mechanisms in cancer cells [
11‐
14]. By inducing autophagy, cancer cells recycle molecules for biosynthetic or metabolic reactions and subsequently tailoring themselves to adverse conditions after anticancer therapy. On the other hand, persistent activation of autophagy can also lead to programmed cell death [
15,
16]. This type of autophagy is irreversible and is termed as type II programmed cell death or autophagic cell death, in contrast to apoptosis, which is referred to type I programmed cell death [
12,
17]. The mechanisms by which autophagy differentially affects tumor cell survival remain to be uncovered.
Malignant gliomas are the most common primary brain tumors in the central nervous system. These tumors increasingly grow and invade into the surrounding brain parenchyma. Despite advances in surgical preventations and treatments, the prognosis of this disease remains poor [
18]. Therefore, developing novel strategies are essential in order to improve effectiveness of treatments for this disease.
In recent years, many compounds that are contained in the diet and beverages have been identified as potential chemopreventive agents. Among them is resveratrol (Res), a natural product highly enriched in grapes, peanuts, red wine, and a wide variety of food sources [
19]. Its exact physiological function is still not known, but it has attracted research attention, owing to its cardioprotective, antioxidant, anti-inflammatory activities and cancer chemopreventive properties [
20,
21]. Res has a number of biological effects in a variety of cell culture systems: it produces variable anti-tumor effects in different tumor cell lines [
19]. Res has been shown to have growth-inhibitory activity, and induces apoptotic cell death in a number of human cancer cell lines as well as in animal models of carcinogenesis. In U251 glioma cells, treatment with Res led to growth inhibition, induction of apoptosis and G0/G1-phase cell cycle arrest [
22]. Res also showed antiproliferative activity in JB6 mouse epidermal, CaCo-2 colorectal and A431 epidermoid carcinoma cell lines [
23‐
25]. Its effects in ovarian cancer cell lines are more complicated. Res can induce ovarian cancer death through two distinct pathways: apoptosis and autophagy [
26]. In the mouse skin carcinogenesis model, Res inhibited the three major steps of carcinogenesis: initiation, promotion, and progression [
19]. In human retinoblastoma cells, Res inhibits cell proliferation and stimulates apoptosis through activation of the mitochondrial apoptotic pathway [
27]. Thus, multiple mechanisms may be activated by Res, depending on the specific cell types and cellular environment. However, the precise role of autophagy in Res's antitumor effects requires further investigation.