Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose‐dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose‐dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP‐ribose) polymerase (PARP) and caspase‐8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK‐mediated pro‐caspases cleavage. Taken together, our results demonstrate that DSK has anti‐cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38‐mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management.

中文翻译：

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脱氧紫草素通过 p38 MAPK 介导的 caspase 激活触发宫颈癌细胞凋亡

脱氧紫草素 (DSK) 是一种生物成分，源自紫草。尽管DSK具有潜在的抗癌活性，但DSK是否对宫颈癌细胞发挥抗癌作用尚不完全清楚。本研究旨在探讨DSK对宫颈癌细胞的抗癌活性及其分子机制。通过MTT测定评估细胞活力。使用蛋白质印迹测定磷酸化和蛋白质的水平。通过特定抑制剂评估信号激酶的参与。我们的结果表明，DSK 以剂量依赖性方式降低人宫颈细胞的活力。同时，DSK显着诱导HeLa和SiHa细胞凋亡。使用细胞凋亡微阵列来阐明所涉及的途径，结果表明，DSK 剂量依赖性地减少细胞凋亡蛋白 1 (cIAP1)、cIAP2 和 XIAP 的抑制剂，并诱导聚 (ADP-核糖) 聚合酶 (PARP) 和胱天蛋白酶-8/9/3。此外，我们观察到 DSK 显着触发 ERK、JNK 和 p38 MAPK (p38) 的激活，并且只有抑制 p38 才能减少 DSK 介导的半胱天冬酶原裂解。综上所述，我们的结果表明，DSK 通过 IAP 下调和 p38 介导的 caspase 激活引发的细胞凋亡级联具有抗宫颈癌作用。这表明 DSK 可以作为促进宫颈癌治疗的佐剂。