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发现一种具有降低ANO1蛋白特性和抗癌潜力的新型天然化合物——维特夸金B。

Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential.

作者信息

Seo Yohan, Lee Sion, Kim Minuk, Kim Dongguk, Jeong Sung Baek, Das Raju, Sultana Armin, Park SeonJu, Nhiem Nguyen Xuan, Huong Phan Thi Thanh, Kwon Oh-Bin, Namkung Wan, Woo Joohan

机构信息

New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation (KMEDIhub), Daegu, Republic of Korea.

Department of Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDI Hub), Daegu, Republic of Korea.

出版信息

Front Pharmacol. 2024 Apr 3;15:1382787. doi: 10.3389/fphar.2024.1382787. eCollection 2024.

Abstract

Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from . Vitekwangin B was chromatographically isolated from the fruits of . ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

摘要

前列腺癌和非小细胞肺癌(NSCLC)在有效治疗策略的开发方面面临重大挑战。前列腺癌的激素疗法以雄激素受体和前列腺特异性抗原标志物为靶点。然而,前列腺小细胞神经内分泌癌的治疗选择有限。另一方面,NSCLC主要用表皮生长因子受体(EGFR)酪氨酸激酶抑制剂治疗,但会出现耐药性。本研究通过研究源自[具体来源未给出]的天然化合物vitekwangin B的潜在抗癌特性,探索了一种新的治疗方法。Vitekwangin B是从[具体植物未给出]的果实中通过色谱法分离得到的。在vitekwangin B处理后,再次验证并评估前列腺癌和NSCLC细胞中的ANO1蛋白水平。Vitekwangin B并未抑制anoctamin1(ANO1)通道功能,但显著降低了ANO1蛋白水平。这些结果表明,vitekwangin B有效抑制了前列腺癌和NSCLC细胞的活力并诱导了细胞凋亡。此外,它对肝细胞的毒性极小,且不影响hERG通道活性,使其成为一种有前景的抗癌药物进一步开发候选物。Vitekwangin B可能通过靶向ANO1蛋白为癌症治疗提供新方向,有望改善前列腺癌和NSCLC患者的治疗效果。需要进一步研究以探索其全部潜力并克服现有的耐药性挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d2/11041392/b818a2449779/fphar-15-1382787-g001.jpg

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