Abstract
Hepatocellular carcinoma (HCC) is the fourth largest cause of cancer-related deaths worldwide with limited therapeutic interventions. Renewed interest in natural products as drug leads has resulted in a paradigm shift toward the rapid screening of medicinal plants for the discovery of new chemical entities. Rotundic acid (RA), a plant-derived triterpenoid, has been anecdotally reported to possess anti-inflammatory and cardio-protective abilities. The present study highlights the anti-cancer efficacy of RA on HCC in vitro and in vivo. The inhibitory effects of RA on HCC cell viability was determined by MTT. Soft agar colony formation and clonogenic assays also showed that RA inhibited HCC cell proliferation. Flow cytometry, confocal, and western blot results further indicated that RA induced cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways. Besides the suppression of migration and invasion, tube formation and VEGF-ELISA revealed the anti-angiogenic abilities of RA on HCC. Moreover, RA also inhibited tumor growth in a HepG2 xenograft mouse model. To our best knowledge, this is the first extensive study of the anticancer activity of RA on HCC. The results demonstrate that RA could be a potential drug candidate for HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is the fourth largest cause of cancer-related deaths worldwide
The IC50 values of Rotundic acid (RA) obtained from the dose survival curves were found to be 34.04 ± 0.58 μM for HepG2 cells (Figure 1C), 62.12 ± 1.16 μM for SMMC-7721 cells (Figure 1D), and 23.25 ± 0.534 μM for human umbilical vein endothelial cells (HUVEC)’s (Figure 1E)
No significant cell death was observed in LO2 cells on RA treatment, indicating that RA had minimal toxic effects on normal hepatic cells as compared to hepatocellular carcinoma (HCC) cells (Figure 1F)
Summary
Hepatocellular carcinoma (HCC) is the fourth largest cause of cancer-related deaths worldwide. Despite recent advances in diagnosis and treatment; poor prognosis, high recurrence, and rapid progression make HCC a highly lethal disease [2]. Angiogenesis, and metastases are the major causes underlying HCC related deaths. Regorafenib, like its predecessor, inhibits receptor tyrosine kinases, their downstream mediators and angiogenesis [8]. These targeted agents improve survival; limited therapeutic benefits and absence of durable responses have led to the suboptimal use of anti-angiogenic therapies [9]. Inefficient therapeutic interventions urge for the rapid development of new therapies for this aggressive disease with the aim of improving treatment response and minimizing toxicity for patients with HCC [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
