Valproic acid suppresses cervical cancer tumor progression possibly via activating Notch1 signaling and enhances receptor-targeted cancer chemotherapeutic via activating somatostatin receptor type II

Abstract

VPA could not only suppress tumor progression but also provide a novel promising therapeutic choice in combination with a receptor-targeted cytotoxic conjugate via activating the specific receptor.

Anti-Convulsant Drug Valproic Acid in Cancers and in Combination Anti-Cancer Therapeutics

“…For instance, VPA could act as a tumor suppressor and up-regulate the SSTR2 that is highly expressed in cervical cancer Hela cells. Based on this, VPA and the SSTR2-targeted conjugate COL-SST, used at much lower doses, display a much more synergitic effect on cervical cancer Hela tumor growth than did each single one given at higher doses [7,43]. Similar results were also observed with the treatment of VPA and another conjugate CPT-SST in Hela tumors in xenografts [9].…”

“…It has been observed that the combination of VPA and the GRPR-targeted CPT-BN conjugate additively suppress in vitro cell proliferation in leukemia MOLT-4, Jurkat cells, osteosarcoma U2OS cells, carcinoid BON cells and CNDT2 cells. We also have observed that the combination of VPA and another SSTR2-targeted CPT-SST conjugate could enhance the cell proliferative suppression in various cancer cells, [9,43]. For instance, VPA could act as a tumor suppressor and up-regulate the SSTR2 that is highly expressed in cervical cancer Hela cells.…”

“…VPA has been used in combination therapeutics with various other compounds, some of which are FDA-approved market drugs [7,8]. These combination treatments display more anti-cancer effects compared to each alone [9,42,43], with some under clinical investigations [7,8,42]. For instance, VPA was used in combination with the topoisomerase I inhibitors Camptothecin (CPT), its new analog irinotecan (CPT-11) or CPT conjugates for treating many cancers such as breast cancer, hepatocellular cancer, cervical cancer, lymphoma, thyroid cancer, pancreatic carcinoid, osteosarcoma and ovarian cancer, displaying synergistic in vitro anti-proliferative and in vivo anti-tumor effects [7,9,44].…”

Valproic acid (VPA) inhibits the epithelial–mesenchymal transition in prostate carcinoma via the dual suppression of SMAD4

“…Khanim and colleagues performed a clinical study on patients with acute myeloid leukemia (AML) and indicated that their clinical response to VPA was relevant to the in vivo level of histone acetylation, the proapoptotic genes, and the genes associated with apoptosis. Furthermore, the sensitivity of cell lines derived from hematologic neoplasms to VPA was closely correlated with FOSB expression in vitro (Tsai et al 2013). SMAD4 plays various roles in different stages of PCa.…”

Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model

“…HDAC inhibition can increase the expression of several genes by accelerating their transcription, which can enhance the innate immune system and lead to suppression of tumor growth. 9,17 VPA alters the expression of various genes involved in the interaction with the cellular immune system, which is known Figure 5. Generation of mouse CIK cells.…”