Abstract
Infantile hemangioma (IH) is a common and benign vascular neoplasms, which has a high incidence in children. Although IH is benign, some patients experience complications such as pain, functional impairment, and permanent disfigurement. Treatment options for IH include corticosteroids, surgery, vincristine, interferon or cyclophosphamide. However, none of these modalities are ideal due to restrictions or potential serious side effects. There is thus a great need to explore novel treatments for IH with less side effects. Angiogenesis, vasculogenesis and tumorigenesis are the main features of IH. Tanshen is mostly used in Chinese traditional medicine to treat hematological abnormalities. Therefore, the aim of our study was to evaluate anti-proliferation and anti-angiogenesis effects on hemangiomas cells by extracted Tanshen compounds compared with propranolol, the first-line treatment for IH currently, both in vitro and in vivo. Cell viability, apoptosis, protein expression and anti-angiogenesis were analyzed by CCK8, Annexin V staining, Western blot and tube formation, respectively. The anti-tumor activity in vivo was evaluated using a mouse xenograft model. Fourteen major compounds extracting from Tanshen were screened for their ability to inhibit hemangiomas cells. Of the 14 compounds investigated, 15,16-Dihydrotanshinone I (DHTS) was the most potent modulator of EOMA cell biology. DHTS could significantly decrease EOMA cells proliferation by inducing cell apoptosis, which is much more efficient than propranolol in vitro. DHTS increased the expression of several apoptosis-related proteins, including caspase9, caspase3, PARP, AIF, BAX, cytochrome c, caspase8 and FADD and significantly inhibited angiogenesis, as indicated by reduced tube formation and diminished expression of vascular endothelial cell growth factor receptor 2 and matrix metalloproteinase 9. In nude mice xenograft experiment, DHTS (10 mg/kg) could significantly inhibit the tumor growth of EOMA cells as well as propranolol (40 mg/kg). Our study showed that DHTS was much more effective than propranolol in inhibiting hemangiomas proliferation and angiogenesis in vitro and in vivo, which could have potential therapeutic applications for treatment of IH.
Highlights
Infantile hemangiomas (IH) is a common and benign vascular neoplasm with an estimated prevalence of 5–10% (Drolet et al, 2005)
All extracted compounds of Tanshen were from Shanghai Institute of Materia Medica (Chinese Academy of Sciences); Captisol was derived from MCE (MedChem Express); Caspase 3, Caspase 8, Caspase 9, Aif, poly (ADP-ribose) polymerase (PARP), Bax, FADD and Cyst3 were all from Abclonal; FITC-Annexin V and PI were from BD Biosciences (Sandiego); Matrigel was from Corning; CCK kit and crystal violet were from Yeasen (China); Nude mice were provided from Shanghai XinHua Hospital
To assess whether Tanshen contains hemangiomas-inhibitory substances, we tested the effect of fourteen main compounds of Tanshen on the EOMA cells, a well-established model for IH study (Gordillo et al, 2002)
Summary
Infantile hemangiomas (IH) is a common and benign vascular neoplasm with an estimated prevalence of 5–10% (Drolet et al, 2005). IH is most common in female, premature, and lowbirth-weight infants (Drolet et al, 2008). These tumors could be solitary or multiple, which undergo rapid growth followed by spontaneous, slow and even incomplete involution for up to 10 years. About 80–95% of the tumors of IH could spontaneously involute, a sort of patients suffer from complications resulting in pain, functional impairment, or permanent disfigurement (Chang et al, 2008; Darrow et al, 2015). The pathogenesis of IH has not been fully elucidated. Epidemiological studies and rare familial cases suggest a genetic influence (Haggstrom et al, 2007)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
