Shikonin induces apoptosis and inhibits migration of ovarian carcinoma cells by inhibiting the phosphorylation of Src and FAK

Hao, Zhenfeng; Qian, Ji; Yang, Jun

doi:10.3892/ol.2014.2771

Cited by 17 publications

(13 citation statements)

References 31 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism associated with shikonin-related anticancer activity is poorly understood. A recent study demonstrated that shikonin inhibits the growth of SKOV3 cells, induces their apoptosis, and reduces their migration through inhibiting the phosphorylation of Src and FAK; these results are consistent with those reported in our study [ 28 ]. Another study also demonstrated the application of shikonin-loaded antibody-armed nanoparticles for targeted therapy in ovarian cancer[ 29 ].…”

Section: Discussionsupporting

confidence: 94%

Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

et al. 2017

View full text Add to dashboard Cite

Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor progression-free survival rates (p = 0.01) as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70–5.85). In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001). We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05) and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.

show abstract

Section: Discussionsupporting

confidence: 94%

Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…2) is an active naphthoquinone, which is derived from the dried root of Lithospermum erythrorhizon, Arnebia euchroma and Arnebia guttata, and it possesses anti-oxidative, anti-inflammatory, and anti-cancer activities [591][592][593][594]. It is effective in treating different kinds of cancers, including breast, prostate, ovarian and thyroid cancers, Ewing sarcoma, and myelomonocytic lymphoma [595][596][597][598][599][600]. Shikonin exerts anti-cancer effects mainly by inducing apoptosis, necroptosis, autophagy, cell cycle arrest, and by inhibiting cell proliferation, growth and metastasis [593,601,602].…”

Section: Shikoninmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

View full text Add to dashboard Cite

Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

show abstract

“…Based on its ability to induce apoptosis in tumor tissue, SK has been widely investigated in cancer treatment [27][28][29][30]. In recent years, the antiapoptotic effects of SK have been gradually discovered in lung injury [31], myocardial ischemic/reperfusion injury [32], osteoarthritis [33], and nervous system diseases [18,20,34].…”

Section: Discussionmentioning

confidence: 99%

Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling

Jia

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Shikonin (SK) exerts neuroprotective effects; however, to date, its protective effect against chronic cerebral hypoperfusion- (CCH-) induced vascular dementia (VaD) has not been investigated. Therefore, the current study investigated whether SK could mitigate the cognitive deficits caused by CCH. The effects of SK treatment on the PTEN/Akt/CREB/BDNF signaling pathway and apoptosis in hippocampal neurons were examined in a rat model of VaD established via bilateral common carotid artery occlusion (BCCAO). Fifty-two rats were randomly divided into 4 groups: sham, vehicle, SK-L (10 mg/kg SK per day), and SK-H (25 mg/kg SK per day). SK was regularly administered by gavage for 2 weeks. The results of the water maze test revealed that the escape latency in the vehicle group was significantly longer than that in the sham group, and rats in the vehicle group spent a smaller proportion of time in the target quadrant than those in the sham group. SK treatment reduced the escape latencies and increased the proportion of time spent in the target quadrant. Nissl staining showed morphological damage in the CA1 areas of the hippocampus in the vehicle group. SK treatment alleviated the injuries to hippocampal neurons. Western blot analysis showed higher p-PTEN and lower p-Akt, p-CREB, and BDNF expression in the vehicle group than in the sham group. SK administration reversed the upregulation of p-PTEN and the downregulation of p-Akt, p-CREB, and BDNF. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling- (TUNEL-) positive cells in the hippocampal CA1 region of the vehicle group was significantly increased. Treatment with SK decreased the number of positive cells. Furthermore, as marker proteins of apoptosis, bcl-2 expression was decreased and bax expression was increased; thus, the ratio of bcl-2/bax was decreased in the vehicle group. SK treatment upregulated the expression of bcl-2 and downregulated the expression of bax, thereby elevating the bcl-2/bax ratio. Moreover, the aforementioned effects of SK were dose-dependent. The effect of 25 mg/kg per day was more obvious than that of 10 mg/kg per day. In conclusion, SK inhibited hippocampal neuronal apoptosis to protect against CCH-induced injury by regulating the PTEN/Akt/CREB/BDNF signaling pathway, consequently improving cognitive impairment.

show abstract

Shikonin induces apoptosis and inhibits migration of ovarian carcinoma cells by inhibiting the phosphorylation of Src and FAK

Cited by 17 publications

References 31 publications

Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling

Contact Info

Product

Resources

About