TABLE 1.
Preclinical status of Withaferin A in cancer.
| Source | Cancer | Potential mechanism | References |
|---|---|---|---|
| Withaferin A | Lung cancer | Cell cycle arrest; decreases PI3K/Akt pathway | Cai et al. (2014) |
| Withaferin A | Lung cancer | Decreased TGF-and TNF- induced EMT; decreased nuclear translocation of Smad 2/3 and NF-κB | Kyakulaga et al. (2018) |
| Withaferin A | Lung cancer | Increased ROS, autophagy, and apoptosis; decreased mTOR/STAT3 signaling | Hsu et al. (2019) |
| Withaferin A | Leukemia | Increased Apoptosis; increased G2/M phase cell cycle arrest and increased ROS | Okamoto et al. (2016) |
| Withaferin A | Glioblastomas | Decreased Cell proliferation; increased G2/M phase cell cycle arrest; increased ROS generation; decreased Akt/mTOR and MAPK pathway | Grogan et al. (2013) |
| Withaferin A | Breast cancer | Decreased mammosphere formation, decreased ALDH1 activity and bCSCs | Kim and Singh (2014) |
| Withaferin A | Breast cancer | Decreased Cell migration, EMT and invasion; decreased IL6 induced STAT3 activation; increased Notch2 and Notch4 and decreased mitochondrial membrane potential | (Widodo et al. 2007; Lee et al. 2010) |
| Withaferin A | Breast cancer | Increased G2/M phase cell cycle arrest and ROS generation and apoptosis, decreased ER-a, XIAP, cIAP-2 and survivin | Lee et al. (2010) |
| Withaferin A | Neuroblastomas | Decreased cell proliferation; increased G0/G1 cell cycle arrest; decreased Cyclin D1 and p-Akt, PSA-NCAM, Bcl-xL, MMP-2, MMP-9 | (Chang et al. 2016; Kataria et al. 2016) |
| Withaferin A | Prostate | Decreased cell proliferation; increased G2/M Phase cell cycle arrest and ROS and autophagy | Nishikawa et al. (2015) |
| Withaferin A | Ovarian cancer | Decreased cell proliferation; increased apoptosis; ROS and G2/M cell cycle arrest; decreased Notch1, Notch2, otch3, Bcl-2, Akt | Fong et al. (2012) |
| Withaferin A | Gastric cancer | Decreased cell viability; increased Apoptosis; G2/M cell cycle arrest and ROS; decreased Cell migration and invasion | Kim et al. (2017) |
| Withaferin A | HFD-induced obese mice and Human Umbilical vein endothelial cells (HUVECs), Mouse, murine fibrosarcoma | Found to be anti-obesity via reduction in COX2, NF-kB, TNF-α, inflammation, insulin resistance and oxidative stress. It was also found to be anti-inflammatory in later models via the downregulation of C- JNK, ERK-1/2, P38, IL-1β like proteins | Heyninck et al. (2014); Abu Bakar et al. (2019) |
| Withaferin A | Human Melanoma cells (M14, Lu1205, SK28) and Breast cancer cell lines (MDA-Mb231 and MCf-7) | Found to be anti-cancerous via upregulation of apoptosis (ROS induced) by decreasing the Bax/Bcl2 and Bcl2/Bim ratio. However, in breast cancer upregulation of caspase-9 and 3 along with PARP was found to be the vital components contributing to anticancer nature of WA. | (Stan et al. 2008a; Mayola et al. 2011) |
| Withaferin A | Xenograft (Breast cancer) and transgenic mice models | Found to be anti-cancerous via upregulation of ERK/RSK axis, DR-5 (death receptor 5), ETS domain containing protein-1, and CAT/CHOP proteins | Nagalingam et al. (2014) |
| Withaferin A | Human Laryngeal Carcinoma (Hep 2 cell line) and Renal cancer (Caki cell line) | Found to be anti-cancerous via downregulation of cell cycle arrest with possible blockage of angiogenesis and downregulation of STAT-3 pathway and upregulation of GRP-78 and CHOP proteins are thought to be main player in Caki cells | Mathur et al. (2006); Choi et al. (2011) |