Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective

Mannan, Ashi; Dhiamn, Sonia; Garg, Nikhil; Singh, Thakur Gurjeet

doi:10.1016/j.ydbio.2023.09.009

Developmental Biology

2023

DOI: 10.1016/j.ydbio.2023.09.009

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Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective

Ashi Mannan,

Sonia Dhiamn,

Nikhil Garg

et al.

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2024

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Cited by 3 publications

References 211 publications

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Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy

Jiang,

Zhang,

Zhang

et al. 2024

Seminars in Cancer Biology

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Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy

Jiang,

Zhang,

Zhang

et al. 2024

Seminars in Cancer Biology

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The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention

Albini,

Noonan,

Corradino

et al. 2024

Cancer Prevention Research

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Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. Since this concept was established in the Seventies, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy and prevention and on substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β-blockers, renin–angiotensin–aldosterone inhibitors, carnitines, and biguanides are reviewed.

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Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress

Hu,

Yang

et al. 2024

Antioxidants

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Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).

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Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective

Cited by 3 publications

References 211 publications

Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy

Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy

The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention

Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress

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