Observe the tolerance of healthy volunteers to shikonin suppositories to determine the safety range of clinical medication and propose dosing regimens and precautions for Phase II clinical trials

Start Date06 Sep 2008

Sponsor / Collaborator

Jilin Institute of Traditional Chinese Medicine

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100 Clinical Results associated with Shikonin Suppository

100 Translational Medicine associated with Shikonin Suppository

100 Patents (Medical) associated with Shikonin Suppository

943

Literatures (Medical) associated with Shikonin Suppository

01 Dec 2024·Molecular Biology Reports

Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation

Article

Author: Liu, Jie ; Liang, Jing ; Wang, Jun ; Ye, Xin ; Chen, Jinghua ; Xie, Qi ; Wang, Xiumei ; Liu, Xiaolin ; Li, Yan

AbstractBackgroundPD-1 blockade has shown impressive clinical outcomes in colorectal cancers patients with high microsatellite instability (MSI-H). However, the majority of patients with colorectal cancer who present low microsatellite instability (MSI-L) or stable microsatellites (MSS) show little response to PD-1 blockade therapy. Here, we have demonstrated that Shikonin (SK) could induce cell death of CT26 cells via classically programmed and immunogenic pathways.Methods and resultsSK promoted the membrane exposure of calreticulin and upregulated the expression of heat shock protein 70 (Hsp70). The upregulation of Hsp70 was dependent on ROS induced by SK and silencing of PKM2 in CT26 cells reverts ROS upregulation. Besides, SK synergizes with PD-1 blockade in CT26 tumor mice model, with the increase of intramural DC cells and CD8+ T cells. The expression of Hsp70 in tumor tissue was also increased in combinational SK plus αPD-1 therapy group.ConclusionsOur study elucidated the potential role of ‘Shikonin-PKM2-ROS-Hsp70’ axis in the promotion of efficacy of PD-1 blockade in CRC treatments, providing a potential strategy and targets for improving the efficacy of PD-1 blockade in colorectal cancer.

01 Dec 2024·Molecular Biology Reports

Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro

Article

Author: Mijatović, Sanja ; Krajnović, Tamara ; Vuković, Nenad L ; Bovan, Dijana ; Tanić, Nikola ; Vukić, Milena D ; Arsenijević, Nebojša ; Maksimović-Ivanić, Danijela

BACKGROUNDShikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6.METHODS AND RESULTSAll examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann-like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death-anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling.CONCLUSIONSHerein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.

07 Oct 2024·Nanotechnology

Enhanced therapeutic impact of Shikonin-encapsulated exosomes in the inhibition of colorectal cancer progression

Article

Author: Liang, Biao ; Yang, Haojie ; Xia, Yubin ; Gong, Yabin ; Wang, Zhenyi ; Han, Changpeng ; Lu, Yuchang ; Li, Ying ; Zhou, Hailun

AbstractColorectal cancer (CRC) is a prevalent malignancy with high mortality rates and poor prognosis. Shikonin (SHK) has demonstrated extensive anti-tumor activity across various cancers, yet its clinical application is hindered by poor solubility, limited bioavailability, and high toxicity. This study aims to develop SHK-loaded exosomes (SHK-Exos) and assess their efficacy in CRC progression. Exosomes were isolated using ultracentrifugation and characterized via TEM, NTA, and western blotting. Their cellular internalization was confirmed through confocal microscopy post PKH67 labeling. Effects on cell behaviors were assessed using CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed via flow cytometry. A xenograft tumor model evaluated in vivo therapeutic potential, and tumor tissues were examined using H&E staining and in vivo imaging. SHK-Exos demonstrated effective cell targeting and internalization in CRC cells. In vitro, SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, while in vivo studies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Employing SHK-Exos effectively impedes CRC progression in vitro and in vivo, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.

100 Deals associated with Shikonin Suppository

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatitis	Phase 1	CN	Jilin Institute of Traditional Chinese Medicine	06 Sep 2008
Prostatitis	Phase 1	CN	Beijing Lingrui Weiya Technology Co. Ltd.	06 Sep 2008

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