Antitumoral effect of Ocoxin in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is becoming one of the most prevalent types of cancer worldwide. The most efficient types of treatment at present include surgical resection and liver transplantation, but these treatments may only be used in a small percentage of patients. In order to identify novel therapeutic strategies for this disease, the present study explored the potential antitumoral effect of Ocoxin® oral solution (OOS) in HCC. OOS inhibited the proliferation of HCC cell lines in a time- and dose-dependent manner, being more efficient when used in combination with sorafenib, a standard of care treatment for patients diagnosed with advanced-stage disease. Mechanistic studies indicated that the effect of OOS was due to the induction of cell cycle arrest rather than the stimulation of apoptotic cell death. The cell cycle was slowed down in all phases in the HCC cell lines treated with OOS. Finally, when tested in animal models of HCC, OOS reduced tumor progression through the induction of necrosis in xenograft tumor models. Considering the poor prognosis and high resistance to antitumor treatments of HCC, the antiproliferative action of OOS, particularly in combination with sorafenib, provides the opportunity to investigate the effect of combined therapy in a clinical setting.

Antitumoral effect of Ocoxin, a natural compound-containing nutritional supplement, in small cell lung cancer

“…Within such a network, one of the actual major players responsible for such anti-proliferative action appears to be the cell cycle inhibitory protein p27. These data corroborate previous studies in which p27 seems to be a key intermediate in OOS anti-proliferative action in other cellular systems such as breast cancer ( 13 ), hepatocarcinoma or acute myeloid leukemia ( 19 , 20 ).…”

“…Given such composition, OOS is currently being investigated in clinical trials as part of the treatment of several types of cancer, demonstrating, to date, an improvement in the quality of life of such patients ( 17 , 18 ). Moreover, several recent studies have investigated the potential antitumor effect of OOS on different tumor models, including HER2-positive breast cancer ( 13 ), acute myeloid leukemia ( 19 ) and hepatocellular carcinoma ( 20 ). In all these models, OOS exhibited clear antitumor properties both in vitro and in vivo in xenograft mouse models.…”

Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin

“…Similarly, OOS has been shown to reduce the proliferation of colon cancer cells and to also reduce the metastatic spreading of tumor cells [16,17]. In addition, OOS has demonstrated antitumoral capability in in vitro and in vivo models of hepatocellular carcinoma [18], small-cell lung cancer [19], and acute myeloblastic leukemia [20]. Mechanistically, the antitumoral action of OOS has been explored using in vitro models.…”

Antitumoral Properties of the Nutritional Supplement Ocoxin Oral Solution: A Comprehensive Review

“…In hepatocellular carcinoma, OOS reduced proliferation in the HepG2 and Huh7 cell lines in a time-and dose-dependent manner [70]. The antitumoral effect of OOS in this model was mainly due to a reduction of cell proliferation without induction of cell death.…”

“…In the breast cancer cell models, down-regulation of cyclin D1 was enhanced if OOS was combined with lapatinib [65], supporting that OOS may increase the efficacy of the latter standard of care drug. In hepatocellular carcinoma, addition of OOS provoked an increase in the amount of cyclin B1 that accompanied cell cycle arrest in G2 [70]. An unbiased microarray study performed on in vivo lung cancer and acute myeloid leukemia cells derived from xenografts prepared in mice, followed by functional transcriptomic evaluation revealed the cell cycle-related functions as the major target functions affected by OOS [66].…”