Propranolol inhibits infantile hemangioma by regulating the miR-424/vascular endothelial growth factor-A (VEGFA) axis

Wu, Zhanxiong; Shi, Senlin; Pan, Feng-Jun; Li, Li; Chen, Hongyu

doi:10.21037/tp-21-244

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…In the early laboratory work with Tanshinone extracts, we discovered that eight Tanshinone monomers could significantly inhibit the proliferation of hemangiomas. Cytological and animal experiments showed that the potency of dihydrotanshinone I (DHTS) was 20 times that of propranolol, and that it differs from the possible mechanism of propranolol ( 20 ). We discovered for the first time that a series of Tanshinone compounds isolated from the fat-soluble extract of Tanshin (Tanshinone extract) have a significant inhibitory impact on the proliferation of hemangioma cells (positive control: propranolol).…”

Section: Discussionmentioning

confidence: 99%

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study

Huang,

Li,

Wang

et al. 2024

Transl Pediatr

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Background Infantile hemangiomas (IHs) on skin are conventionally treated with beta blockers, pulsed dye laser (PDL), or surgery, either invasive or limited to clinical conditions. Our preclinical studies suggested that Tanshinone, extracted from Salvia miltiorrhiza (Tanshin), had a beneficial effect on IHs. Thus, we conducted a pilot clinical study to evaluate the safety and efficacy of topical Tanshinone compounds on superficial IHs. Methods The single-armed pilot study included a total of 29 infants diagnosed with IHs. Thrice daily (at an interval of 6–8 hours) topical applications of Tanshinone were used for each patient. The primary response was the skin erythema index assessed by investigators using SkinColorCatch colorimeter instrument (Delfin). The Achauer score and the satisfaction of parents were also evaluated. Results A total of 29 infants, 22 females (76%) and 7 males (24%), with a median age of 60 days (interquartile range, 45 to 99 days) were included. The position of IHs was distributed in the trunk (44.8%), head (34.5%), and limbs (20.7%). After 6 months of IHs treatment, the decrease in skin erythema index (baseline: 566.79±854.67 vs. after treatment: 467.97±1,118.39, P<0.001) was indicated. A total of 79.31% [23/29] of parents of the participants reported satisfaction on the responses after treatment. No serious side effects were documented. Conclusions The topical use of Tanshinone compounds might be a potentially effective and noninvasive therapy in treating IHs.

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Section: Discussionmentioning

confidence: 99%

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study

Huang,

Li,

Wang

et al. 2024

Transl Pediatr

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“…The mechanism may be related to the inhibition on the migration of hemangioma endothelial cells, network formation, VEGF-A production, activation of vascular endothelial growth factor receptor 2, and downregulation of the PI3K/Akt and mitogen-activated protein kinase signals. [8][9][10][11] However, regarding whether changes in cytokines in the body affect children's growth and development, there are currently literature reports on monitoring the physical development results of children taking medication, such as height and weight. Tang et al [12] found that oral propranolol treatment for infantile hemangioma children had a certain impact on physical development indices in a study of 116 such children.…”

Section: Discussionmentioning

confidence: 99%

The impact of propranolol on the growth and development of children with proliferative infantile hemangioma during treatment

et al. 2023

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Oral propranolol has not been shown to impact physical development, such as weight and height. The impact of children’s intellectual development has received relatively little attention from researchers. The effects of propranolol on the growth and development of children with proliferative infantile hemangiomas during treatment were analyzed retrospectively. The children with infantile hemangioma treated with oral propranolol in the Department of Burn and Plastic Surgery, Fuzhou Children’s Hospital of Fujian Province, from February 2017 to May 2022 were analyzed. A uniform therapeutic regimen was applied, including assessment, treatment, and follow-up. The assessment included physical development and intellectual development indices. The physical development indices were height and weight. Neuropsychological assessment uses developmental quotient (DQ) to assess intelligence development. The DQs on months 3, 6, and 9 posttreatment were compared to the pretreatment. Wilcoxon rank sum test of paired samples was used for height and weight. The developmental quotient was determined by paired t test. P < .05 indicated significant difference. A total of 51 patients were enrolled. All children completed the treatment successfully, without severe adverse drug reactions leading to treatment discontinuation. There was no significant difference in height and weight before and after treatment (P > .05). No significant difference was detected in DQ 3 months posttreatment and pretreatment (P = .19), while it decreased at 6 and 9 months posttreatment (P < .05). Oral propranolol does not have an impact on physical development (height and weight). No short-term effect was found on intellectual development, but a decrease was noted over 6 months, which needs to be investigated further.

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“…Previous studies have shown that propranolol inhibits the angiogenesis of normal endothelial cells, as well as the angiogenesis of hemangioma ( Chim et al, 2012 ; Lamy et al, 2010 ). It has also been shown that propranolol inhibits the proliferation and induces the apoptosis of endothelial cells within hemangioma, which was mediated by the suppression of vascular endothelial growth factor A (VEGFA) expression ( Tavakoli et al, 2017 ; Wu et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma

Wang

Chen

Yang

et al. 2023

PeerJ

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Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.

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Propranolol inhibits infantile hemangioma by regulating the miR-424/vascular endothelial growth factor-A (VEGFA) axis

Cited by 10 publications

References 22 publications

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study

The impact of propranolol on the growth and development of children with proliferative infantile hemangioma during treatment

Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma

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