| The antitumor effect of Cryptotanshinone. Cryptotanshinone can induce the apoptosis of cancer cells by inhibiting PI3K/AKT, STAT3 signaling pathways, as well as transcription of MMP14, STAT3, and Nrf2 genes. The arrow represents the upregulation, and the T area represents the downregulation.

| The antitumor effect of Cryptotanshinone. Cryptotanshinone can induce the apoptosis of cancer cells by inhibiting PI3K/AKT, STAT3 signaling pathways, as well as transcription of MMP14, STAT3, and Nrf2 genes. The arrow represents the upregulation, and the T area represents the downregulation.

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Cancer is among the most life-threatening diseases worldwide. Along with conventional therapies like chemotherapy, surgery, and radiotherapy, alternative treatment approaches such as traditional Chinese medicine have attracted considerable public and scientific interest that could be beneficial for patients diagnosed with cancer. Salvia miltiorrhiz...

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... reported by Wang et al. (2017), CPT can act in a dosedependent manner to prevent migration and proliferation of TSCC (tongue squamous cell carcinoma) cells and trigger apoptosis in them by suppressing the expression of p-STAT3, Bcl-2, CDK2, Snail, and MMP2 and inducing the expression of E-cadherin, P53, P21, and β-catenin. Furthermore, the combined treatment of paclitaxel and CPT has been found to have similar effects to CPT through inhibiting the STAT3 signaling pathway (anticancer potential of Cryptotanshinone is summarized in Figure 1). ...

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... 3 Cryptotanshinone (CPT) is one of the main tanshinone compounds (accounting for about 30% of the total tanshinones), with anti-tumor, anti-inflammatory, cardiovascular protection, anti-fibrosis, and anti-metabolic disorder properties. [4][5][6][7] CPT can inhibit the proliferation of a variety of cancer cells, such as lung cancer, gastric cancer, liver cancer, and bladder cancer, as well as CRC. 8 It is reported that CPT intervenes in the progression of CRC, including proliferation and angiogenesis. 9 In CRC cells (SW620/AD300), CPT overcame P-glycoprotein (P-gp)-mediated multidrug resistance by decreasing P-gp mRNA and protein expression, which in turn inhibited P-gp ATPase activity, resulting in increased toxicity of doxorubicin to SW620/AD300 cells. ...
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Cryptotanshinone (CPT) is the main pharmacologically active component of Salvia miltiorrhiza Bunge, and has been demonstrated to have inhibitory effects on a variety of cancer cell types. However, the target(s) of CPT in colorectal cancer (CRC) cells are still to be identified. The aim of this study was to investigate the molecular mechanism of CPT-induced apoptosis in CRC cells. Transcriptome sequencing revealed that 1234 genes were differentially expressed in CPT-treated SW480 cells compared with vehicle control, which were associated with signaling pathways such as PI3K/AKT, Pathways in cancer and biological processes include cell proliferation and mitochondrial function. CCK-8, colony formation assay, and CRC tumor xenograft models suggested that CPT suppressed the colony formation ability and inhibited proliferation of CRC cells in vitro and in vivo, while flow cytometry indicated that CPT arrested the cell cycle in S phase. JC-1, Hoechst and Western blot analysis indicated that CPT promoted apoptosis in CRC cells and triggered alterations in mitochondrial membrane potential. In addition, database analysis showed that high SIRT3 expression in CRC and high SIRT3 expression in CRC was associated with shorter survival times. Immunofluorescence, Western blot, and molecular docking confirmed that CPT was able to target SIRT3 and downregulate SIRT3 protein levels in a concentration-dependent manner. In summary, CPT inhibits SIRT3 protein expression and inhibits CRC proliferation in vitro and in vivo.
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Background: Cryptotanshinone (CPT), a Traditional Chinese Medicine (TCM) has recently gained remarkable interest as a potent alternative cancer therapeutic. The sole objective of this review is to accumulate the antitumour activity of CPT against major cancers as well as the underlying mechanisms. Methods: This comprehensive review focuses on the experimental outcome of in vivo and in vitro investigations targeting multiple signalling pathways of various cancers and molecular mechanisms involved in hindering cancer growth. Results: CPT targets different cell signalling pathways, transcription factors (STAT1, 3, 4, 5, c-Myc), cellular markers (PD-1, CTLA-4, PDL-1), kinases (Tyrosine kinase such as IGF-1R, Bcr-Abl, Src, JAK, FAK, Serine/Threonine kinase such as Aurora A, Cyclin dependent kinase such as CDK1, 2) which are associated with stemness, growth, division, proliferation, metastasis, angiogenesis and drug resistance of a cancer cell. CPT suppresses cancer progression by inhibiting the phosphorylation of intermediate signalling molecules like STAT3, hence disrupting the STAT3 signalling pathway amongst several other signalling pathways involved in cancer progression. CPT may also induce apoptosis by modulating several pro-apoptotic (Bax, Bak, Bcl-10) and antiapoptotic (Bcl-2, Bcl-x, Bcl-xL) proteins. Furthermore, CPT showed potential drug synergism with other chemotherapeutic drugs resulting in strategizing better cancer treatment. Conclusion: This review summarizes that CPT, being a natural product with less side-effects in long-term cancer use, may be considered as a potential alternative to the traditional cancer therapies. Although, there is substantial evidence of success in laboratory, its efficacy for clinical application may be increased with an appropriate drug delivery approach and the accurate formulation or dosage.