TABLE 2.
Various cellular effects and molecular targets of resveratrol nanoformulations involved in carcinogenesis
| Cancer | Molecular targets | Cellular effects | Cell line | Reference |
|---|---|---|---|---|
| Skin cancer | G1/S arrest. Downregulation of Bcl‐2, Bcl‐xL proteins | Inhibition of NF‐kB signaling pathway | SK‐Mel‐28 and Colo‐38 | 89 |
| S‐phase arrest and decrease in G2/M phase | Inhibition of cell division | A375 | 95 | |
| Avoid metastasis and pulmonary hemorrhage | Increased necrotic area and inflammatory infiltrate of melanoma tumor | B16F10 | 96 | |
| Breast cancer | Downregulation of MMP‐9, COX‐2, NF‐kB protein | Inactivation of PI3K/AKt and ERK1/2 and activation of HO‐1 signaling cascade | MCF‐7 | 97 |
| G0/G1 arrest, upregulation of Bax and downregulation of cyclin D1, c‐Myc, and Bcl‐2/Bax ratio | Induction of apoptosis and Wnt signaling pathway | MDA‐MB‐231 | 98 | |
| Downregulation of BCL‐xl, MMP‐9 and HER‐2. Cell cycle arrest at G2/M phase | Induction of apoptosis and inhibition of HRG‐β1 signaling pathway | T47D and MCF‐7 | 99 | |
| Suppression of VEGF, CD‐1, aromatase, NF‐kB, and elevation of caspase‐3 | Induction of apoptosis, reduction of cell proliferation, and inhibition of PI3K/Akt pathway | MCF‐7 | 84 | |
| Prostate cancer | Reduced expression of Akt protein | Inhibition of microRNA21/Akt signaling pathway | DU‐145, PC3, LNCaP | 50 |
| Downregulation of NF‐kB, p65, COX‐2, BCL‐2, BCL‐XL, survivin, and upregulation of caspase‐3, BAX, BAK | Inhibition of NF‐kB pathway | PC3, C4‐2B, and LNCaP | 13 | |
| Cell cycle arrest at G1‐S transition phase and upregulation of caspase‐3 | Induction of apoptosis | LNCaP | 100 | |
| Increased expression of P53. Reduced expression of MMP‐2 and MMP‐9 and controls angiogenesis | Induction of apoptosis | DU145 | 82 | |
| Downregulation of Bcl‐2 expression | Induction of apoptosis | PC‐3 | 101 | |
| Downregulation of p‐Akt, cyclin D1, and m‐TOR proteins | Induction of apoptosis and inhibition of AR/mTOR signaling pathway | PTEN‐CaP8 | 102 | |
| Colon cancer | Decreased expression of intracellular apoptotic protein I (cIAP1) | Inhibition of NF‐kB signaling pathway | HT‐29 and LS147T | 103 |
| Downregulation of cyclin D1 | Induction of apoptosis and cell necrosis PI3K/PTEN/Akt pathway | BGC823 and SGC‐7901 | 91 | |
| Downregulation of NF‐kB and IL‐6 | Induction of apoptosis | RAW 264.7 and Caco‐2 | 104 | |
| Dose‐dependent increase in caspase‐3 and PARP | Induction of apoptosis through activation of P53 | CT26 | 105 | |
| Liver cancer | Modulates NO/NOS by upregulating the NO production and NOS activity | Induction of apoptosis and inhibition of PI3K/Akt signaling pathway | SMMC 7721 and L02 | 106 |
| Lung cancer | Upregulation of Bax, p53, p21, caspase‐3 and downregulation of Bcl‐2 and NF‐kB proteins | Induction of apoptosis and cell cycle arrest in G0/G1 phase | NCI‐H460 | 107 |
| Upregulation of caspase‐9 and caspase‐3 | Induction of apoptosis in both non‐resistant and resistant cancer cells via mitochondria‐dependent signaling pathway | A549 | 108 | |
| Increased intracellular ROS generation and DNA damage | Activation of p53 dependent apoptotic cascade | NCI‐H460 | 109 | |
| Upregulation of caspase‐3 and reduced expression of Ki‐67 and VEGF | Induction of apoptosis and inhibition of angiogenesis | A549 | 93 | |
| Ovarian cancer | Dose‐dependent induction of apoptosis and activation of caspase‐3 | Apoptosis inducing factor (AIF) apoptosis pathway | SKOV3 | 110 |
| Increased expression of caspase‐3 | Induction of apoptosis | ES2‐luc, A2780 | 94 | |
| Upregulation of Bax, caspase‐9, and downregulation of Bcl‐2 | Induction of apoptosis via ROS generation and targeting through mitochondria mediated pathway | PA1 | 111 |
Abbreviations: COX‐2, Cyclooxygenase‐2; ERK1/2, extracellular signal regulated kinases; HER‐2, human epidermal growth factor receptor 2; HERG‐β1, heregulin‐beta 1; HO‐1, hemeoxygenase‐1; MAPK, mitogen‐activated protein kinases; MMP‐9, matrix metalloproteinase‐9; mTOR, mammalian target of rapamycin; NF‐kB, nuclear factor kappa; NO, nitric oxide; NOS, nitric oxide synthase; PARP, Poly(ADP‐ribose) polymerase; PI3K/Akt, Phosphatidlyinositol‐3kinase; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor.