Deoxyshikonin triggers apoptosis in cervical cancer cells through p38 MAPK-mediated caspase activation.

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.

Shikonin in breast cancer treatment: a comprehensive review of molecular pathways and innovative strategies.

OBJECTIVES: Breast cancer is a prevalent disease that has a substantial impact on women's mortality rates. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, has demonstrated substantial anticancer effects. This study aims to conduct a comprehensive review of the latest research findings regarding the therapeutic efficacy of shikonin in the context of breast cancer treatment, with a specific emphasis on elucidating the underlying molecular mechanisms. METHODS: A comprehensive literature review was conducted on shikonin and breast cancer by searching PubMed, Scopus, Web of Science, and Google Scholar databases. KEY FINDINGS: Shikonin significantly reduces tumor cell viability, proliferation, migration, invasion, and metastasis in both in vivo and in vitro across all breast cancer subtypes. Additionally, when combined with other pharmaceutical agents, it exhibits synergistic effects. Shikonin stimulates immunogenic cell death, resulting in apoptosis and necroptosis. The induction of immunogenic cell death by shikonin enhances the immunogenicity of breast cancer cells, leading to its involvement in the development of dendritic cell-based tumor vaccines against breast cancer. CONCLUSION: Shikonin exhibits potent anti-breast cancer properties and shows significant potential for the advancement of immunotherapeutic approaches against breast cancer, as well as enhancing the efficacy of conventional treatment strategies.