Identification of new natural compounds against KSHV-related malignancies

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 <i>in vivo</i>. 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.