Sinha Krishnendu, Chowdhury Sayantani, Banerjee Sharmistha, Mandal Bhagirath, Mandal Mullicka, Majhi Sasadhar, Brahmachari Goutam, Ghosh Jyotirmoy, Sil Parames C
Department of Zoology, Jhargram Raj College, Jhargram, 721507, West Bengal, India.
Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, 700054, West Bengal, India.
Heliyon. 2019 Aug 2;5(8):e02107. doi: 10.1016/j.heliyon.2019.e02107. eCollection 2019 Aug.
Renal cell carcinoma (RCC) is the most common kidney cancer leading to 140,000 deaths per year. Among all RCCs 80% evolve from the epithelial proximal tubular cells within the kidney. There is a high tendency of developing chemoresistance and resistance to radiation therapy in most RCC patients. Therefore, kidney resection is considered as the most effective treatments for patients having localized RCC. There is a high tendency of post-operative recurrence among 20-40% of the patients and this recurrence is not curable. It is also clear that modern medicine has no curative treatment options against metastatic RCC. Lupeol [lup-20(29)-en-3β-ol] is a pentacyclic triterpenoid compound naturally found in various edible fruits and in many traditionally used medicinal plants, and has been demonstrated as effective against highly metastatic melanoma and prostate cancers. The present study was designed to evaluate the effect of lupeol to RCC with molecular details. Treatment with lupeol on SK-RC-45 (a RCC cell line) with the LC dose of 40μM (for 48 h) induces mitochondrial hyper fission which eventually leads to apoptosis while SK-RC-45 counteracts by enhancing autophagy-mediated selective removal of fragmented mitochondria. This is the first study which concurrently reports the effects of lupeol on RCC and its effect on the mitochondrial dynamics of a cell. Herein, we conclude that lupeol has potential to be an effective agent against RCC with the modulation of mitochondrial dynamics.
肾细胞癌(RCC)是最常见的肾癌,每年导致14万人死亡。在所有肾细胞癌中,80%起源于肾内的上皮近端小管细胞。大多数肾细胞癌患者有很高的发生化疗耐药和放疗抵抗的倾向。因此,肾切除术被认为是局限性肾细胞癌患者最有效的治疗方法。20%-40%的患者术后复发倾向很高,且这种复发无法治愈。同样明显的是,现代医学对转移性肾细胞癌没有治愈性的治疗选择。羽扇豆醇[lup-20(29)-en-3β-ol]是一种五环三萜类化合物,天然存在于各种可食用水果和许多传统药用植物中,并已被证明对高转移性黑色素瘤和前列腺癌有效。本研究旨在详细从分子层面评估羽扇豆醇对肾细胞癌的作用。用40μM的LC剂量(处理48小时)的羽扇豆醇处理SK-RC-45(一种肾癌细胞系)会诱导线粒体过度分裂,最终导致细胞凋亡,而SK-RC-45通过增强自噬介导的对破碎线粒体的选择性清除来对抗。这是第一项同时报道羽扇豆醇对肾细胞癌的作用及其对细胞线粒体动力学影响的研究。在此,我们得出结论,羽扇豆醇有潜力通过调节线粒体动力学成为一种有效的抗肾细胞癌药物。