Chen Jungang, Fan Jiaojiao, Dai Lu, Qin Zhiqiang
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences 4301 W Markham St, Little Rock, AR 72205, USA.
Am J Cancer Res. 2025 May 15;15(5):2170-2179. doi: 10.62347/VBVM8666. eCollection 2025.
Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's Sarcoma (KS) and Primary Effusion Lymphoma (PEL), which preferentially arise in immunocompromised patients and lack of effective therapeutic options. Increasing evidence has supported that many natural products from plants or other resources display anticancer activities, whereas only limited data reported them in the treatment of KSHV-related malignancies. In the current study, we identified 7 natural compounds displaying prominent anti-KS and anti-PEL activities after high-throughput screening of a natural compound library on TIVE-LTC and BCBL-1 cell lines, respectively. Remarkably, most of these compounds showed much less or no toxicity on normal cells. Some of these natural compounds effectively repress PEL expansion . RNA-Sequencing and functional validation assays revealed the anticancer mechanisms of these new compounds, and identified new cellular factors such as FN1 which is required for PEL survival and growth. Taken together, our study provides promising new directions for fighting these virus-associated malignancies.
卡波西肉瘤相关疱疹病毒（KSHV）是多种人类癌症的病原体，包括卡波西肉瘤（KS）和原发性渗出性淋巴瘤（PEL），这些癌症优先发生在免疫功能低下的患者中且缺乏有效的治疗选择。越来越多的证据支持，许多来自植物或其他来源的天然产物具有抗癌活性，然而只有有限的数据报道了它们在治疗KSHV相关恶性肿瘤方面的作用。在本研究中，我们通过分别在TIVE-LTC和BCBL-1细胞系上对天然化合物文库进行高通量筛选，鉴定出7种具有显著抗KS和抗PEL活性的天然化合物。值得注意的是，这些化合物中的大多数对正常细胞显示出低得多的毒性或无毒性。其中一些天然化合物有效地抑制了PEL的增殖。RNA测序和功能验证试验揭示了这些新化合物的抗癌机制，并鉴定出了诸如FN1等PEL存活和生长所需的新细胞因子。综上所述，我们的研究为对抗这些病毒相关恶性肿瘤提供了有前景的新方向。
