Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice

Abstract

Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments.

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

“…In breast cancer, THC showed notable cytotoxicity and anti-proliferation and promoted apoptosis through the mitochondrial pathway [ 29 ]. Similarly, THC inhibited the expression of cyclooxygenase-2 and epidermal growth factor receptor to slow down the growth and development of cervical cancer in nude mouse models [ 30 ]. OS cells are mesenchymal in nature and normally differentiate into osteoblastic lineage.…”

Tetrahydrocurcumin‑induced autophagy via suppression of PI3K/Akt/mTOR in non‑small cell lung carcinoma cells

“…THC has anti-inflammatory, antioxidative and antitumor effects (7)(8)(9)(10)(11)(12). Previous studies have revealed that THC inhibits the invasion of breast cancer (10,18).…”

“…THC has a β-diketone structure and two phenolic groups ( Fig. 1) and has anti-inflammatory, antioxidative and antitumor properties (7)(8)(9)(10)(11)(12); treatment of NSCLC via THC requires further investigation.…”

Schiff Bases of Tetrahydrocurcumin as Potential Anticancer Agents

“…The white coloured THC can also be synthesized in laboratory through hydrogenation of curcumin and has shown potent biological activities including antioxidant, antiinlfammatory and anticancer properties . THC shows significant inhibitory effect against human breast cancer MCF‐7 cells, tumor metastasis and tumor angiogenesis, and is a potent chemo‐preventive agent against colon carcinogenesis . Furthermore, THC is an inhibitor of P‐glycoprotein, and has been explored as a potential way to overcome multidrug resistance in cancer …”