2,3-Dihydro-3β-methoxy withaferin-A (3βmWi-A) is a natural withanolide that is structurally close to withaferin-A (Wi-A), is cytotoxic to human cancer cells, and is a candidate anticancer natural compound. Using cell-based biochemical, molecular, and imaging assays, we report that Wi-A and 3βmWi-A possess contrasting activities. Whereas Wi-A caused oxidative stress to normal cells, 3βmWi-A was well tolerated at even 10-fold higher concentrations. Furthermore, it promoted survival and protected normal cells against oxidative, UV radiation, and chemical stresses. We provide molecular evidence that 3βmWi-A induces antistress and pro-survival signaling through activation of the pAkt/MAPK pathway. We demonstrate that 3βmWi-A (i) contrary to Wi-A is safe and possesses stress-relieving activity, (ii) when given subsequent to a variety of stress factors including Wi-A, protects normal cells against their toxicity, and (iii) is a vital compound that may guard normal cells against the toxicity associated with various targeted therapeutic regimes in clinical practice.

中文翻译：

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2,3-二氢-3β-甲氧基枯草杆菌素A保护正常细胞免受压力：其有效的细胞保护活性的分子证据。

2,3-二氢-3β-甲氧基枯草杆菌素A（3βmWi-A）是一种天然的山梨醇化物，在结构上与枯草菌素A（Wi-A）接近，对人癌细胞具有细胞毒性，并且是候选的抗癌天然化合物。使用基于细胞的生化，分子和成像分析，我们报告Wi-A和3βmWi-A具有对比活性。Wi-A对正常细胞造成氧化应激，而3βmWi-A甚至在高10倍的浓度下也具有良好的耐受性。此外，它可以提高存活率并保护正常细胞免受氧化，紫外线辐射和化学胁迫的侵害。我们提供分子证据，证明3βmWi-A通过激活pAkt / MAPK途径诱导抗应激和促生存信号。我们证明了与Wi-A相反的3βmWi-A（i）是安全的，并且具有缓解压力的功能，