Novel Antimitotic Agent SP-1-39 Inhibits Head and Neck Squamous Cell Carcinoma.

Journal of dental research Pub Date : 2024-08-01 Epub Date: 2024-08-05 DOI:10.1177/00220345241261982
K L Adeleye, A R Li, Y Xie, S Pochampally, D Hamilton, F Garcia-Godoy, D D Miller, W Li
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Abstract

Effective management of head and neck cancer (HNC) poses a significant challenge in the field of oncology, due to its intricate pathophysiology and limited treatment options. The most common HNC malignancy is head and neck squamous cell carcinoma (HNSCC). HNSCC treatment includes a combination of surgery, radiation, and chemotherapy. While HNSCC is treatable if diagnosed early, this is often not the case and is considered incurable once in its late stages and metastatic disease has developed. Therapies are also limited once resistant disease has occurred. SP-1-39, a novel colchicine-binding site inhibitor (CBSI), has been recently reported for its potential efficacy in a variety of cancer cell lines including breast, melanoma, pancreatic, and prostate. SP-1-39 also shows abilities to overcome paclitaxel resistance in a paclitaxel-resistant prostate cancer xenograft model. To evaluate the potential of SP-1-39 as a new HNSCC treatment option, herein we systematically performed preclinical studies in HNSCC models using SP-1-39 and demonstrated that, in vitro, SP-1-39 inhibits the proliferation of 2 HNSCC cell lines with low nanomolar IC50 values (1.4 to 2.1 nM), induces HNSCC cell apoptosis in a dose-dependent manner, interferes with migration of HNSCC cells, and leads to HNSCC cell cycle arrest in the G2/M phase. In vivo, SP-1-39 suppresses the primary tumor growth of a Detroit 562 subcutaneous xenograft mouse model in 6- to 8-wk-old, male NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, with no detectable cytotoxic effects at a low dose of 2.5 mg/kg. This efficacy of SP-1-39 is better when compared with the treatment using a reference chemotherapy drug, paclitaxel at 10 mg/kg. Collectively, these data demonstrate that SP-1-39 is a promising candidate for further development for more efficacious HNSCC treatment.

新型抗溃疡剂 SP-1-39 抑制头颈部鳞状细胞癌
头颈癌(HNC)的病理生理学错综复杂,治疗方案有限,因此有效治疗头颈癌是肿瘤学领域的一项重大挑战。最常见的 HNC 恶性肿瘤是头颈部鳞状细胞癌(HNSCC)。HNSCC 的治疗包括手术、放疗和化疗。虽然 HNSCC 在早期诊断的情况下是可以治疗的,但情况往往并非如此,一旦进入晚期并出现转移性疾病,就会被认为是无法治愈的。一旦出现耐药性疾病,治疗方法也会受到限制。SP-1-39 是一种新型秋水仙碱结合位点抑制剂 (CBSI),最近有报道称它对乳腺癌、黑色素瘤、胰腺癌和前列腺癌等多种癌症细胞系具有潜在疗效。SP-1-39 还能在紫杉醇抗性前列腺癌异种移植模型中克服紫杉醇抗性。为了评估 SP-1-39 作为一种新的 HNSCC 治疗方案的潜力,我们在此使用 SP-1-39 对 HNSCC 模型进行了系统的临床前研究,结果表明,在体外,SP-1-39 能以较低的纳摩尔 IC50 值(1.4 至 2.1 nM)抑制 2 种 HNSCC 细胞株的增殖,以剂量依赖性方式诱导 HNSCC 细胞凋亡,干扰 HNSCC 细胞的迁移,并导致 HNSCC 细胞周期停滞在 G2/M 期。在体内,SP-1-39 可抑制 Detroit 562 皮下异种移植小鼠模型中 6 至 8 周大雄性 NSG(NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)小鼠的原发性肿瘤生长,在 2.5 毫克/千克的低剂量下没有检测到细胞毒性作用。与使用参考化疗药物紫杉醇(10 毫克/千克)进行治疗相比,SP-1-39 的疗效更好。这些数据共同表明,SP-1-39 是一种有望进一步开发的候选药物,可用于更有效的 HNSCC 治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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