Swetha Mundanattu, Keerthana Chenicheri K, Rayginia Tennyson P, Nath Lekshmi R, Haritha Nair Hariprasad, Shabna Anwar, Kalimuthu Kalishwaralal, Thangarasu Arun K, Aiswarya Sreekumar U, Jannet Somaraj, Pillai Sreekumar, Harikumar Kuzhuvelil B, Sundaram Sankar, Anto Nikhil Ponnoor, Wu Dee H, Lankalapalli Ravi S, Towner Rheal, Isakov Noah, Deepa Sathyaseelan S, Anto Ruby John
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, India.
Department of Biotechnology, University of Kerala, Thiruvananthapuram 695011, Kerala, India.
Pharmaceuticals (Basel). 2022 May 22;15(5):636. doi: 10.3390/ph15050636.
We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from Linn, against HCC. Recently, the U.S. FDA approved Utt-B as an 'orphan drug' against HCC. The current study validates the superior anti-HCC efficacy of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib, Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus, be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.
我们之前报道了从[植物名称]中分离并在我们实验室鉴定出的乌索苷B（Utt-B）对肝癌具有显著的效力。最近，美国食品药品监督管理局（FDA）批准乌索苷B作为治疗肝癌的“孤儿药”。本研究验证了乌索苷B相对于索拉非尼（肝癌一线治疗药物）具有更优的抗肝癌疗效。在体外，使用多种肝癌细胞系，以及在体内，利用携带人肝癌异种移植瘤的NOD.CB17-Prkdcscid/J小鼠，比较了乌索苷B与索拉非尼对肝癌的治疗效果。我们的数据表明，乌索苷B比索拉非尼具有更强的抗肝癌疗效。我们之前的报告证明了即使在乌索苷B浓度升高的情况下，其在正常永生化肝细胞Chang Liver以及急性和慢性毒性小鼠模型中的药理安全性。在这里，我们表明，较高浓度的索拉非尼在Chang Liver以及急性和慢性体内模型中会诱导严重毒性，这表明，除了比索拉非尼具有更好的治疗效果外，乌索苷B是一种药理安全性更高的分子，因此，在肝癌化疗中可以显著减轻药物引起的不良影响。在肝癌患者中使用乌索苷B进行临床研究，是将该药物推向临床的关键一步。
