Curcumin improves the paclitaxel-induced apoptosis of HPV-positive human cervical cancer cells via the NF-κB-p53-caspase-3 pathway

Abstract

Paclitaxel, isolated from Taxus brevifolia, is considered to be an efficacious agent against a wide spectrum of human cancers, including human cervical cancer. However, dose-limiting toxicity and high cost limit its clinical application. Curcumin, a nontoxic food additive, has been reported to improve paclitaxel chemotherapy in mouse models of cervical cancer. However, the underlying mechanisms remain unclear. In this study, two human cervical cancer cell lines, CaSki [human papilloma virus (HPV)16-positive] and HeLa (HPV18-positive), were selected in which to investigate the effect of curcumin on the anticancer action of paclitaxel and further clarify the mechanisms. Flow cytometry and MTT analysis demonstrated that curcumin significantly promoted paclitaxel-induced apoptosis and cytotoxicity in the two cervical cell lines compared with that observed with paclitaxel alone (P<0.05). Reverse transcription-polymerase chain reaction indicated that the decline of HPV E6 and E7 gene expression induced by paclitaxel was also assisted by curcumin. The expression levels of p53 protein and cleaved caspase-3 were increased significantly in the curcumin plus paclitaxel-treated HeLa and CaSki cells compared with those in the cells treated with paclitaxel alone (P<0.01). Significant reductions in the levels of phosphorylation of IκBα and the p65-NF-κB subunit in CaSki cells treated with curcumin and paclitaxel were observed compared with those in cells treated with paclitaxel alone (P<0.05). This suggests that the combined effect of curcumin and paclitaxel was associated with the NF-κB-p53-caspase-3 pathway. In conclusion, curcumin has the ability to improve the paclitaxel-induced apoptosis of HPV-positive human cervical cancer cell lines via the NF-κB-p53-caspase-3 pathway. Curcumin in combination with paclitaxel may provide a superior therapeutic effect on human cervical cancer.

Lin28B is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

“…Several studies have shown curcumin to be a promising sensitizer to chemotherapeutic agents, including paclitaxel, in a wide variety of tumor cell types (Kumar et al, 2017; Zhang et al, 2017; Zou et al, 2018; Dang et al, 2015; Lu et al, 2017; Zhan et al, 2014). Curcumin combined with standard docetaxel chemotherapy led to a significant improvement and clinical response in patients with metastatic breast cancer in a phase I clinical trial (Bayet-Robert et al, 2010).…”

“…Curcumin combined with standard docetaxel chemotherapy led to a significant improvement and clinical response in patients with metastatic breast cancer in a phase I clinical trial (Bayet-Robert et al, 2010). Considering the pleiotropic activity of curcumin in cancer prevention, it could be involved in chemosensitization in several different ways, such as inhibition of NF-κB signaling (Dang et al, 2015), miRNA-induced suppression of cell proliferation (Lu et al, 2017), and modulation of epidermal growth factor receptor (EGFR) signaling (Zhan et al, 2014). Our results showed that Lin28B expression in Hep3B/TAX cells and xenograft tumor tissue was significantly decreased in a dose-dependent manner following co-treatment with curcumin and paclitaxel.…”

An update on Curcuma as a functional food in the control of cancer and inflammation

“…These antineoplastic and apoptotic effects were enhanced when diclofenac and curcumin were administered together, rather than individually [7 && ]. In a recently published paper [8], curcumin demonstrated the ability to improve the paclitaxel-induced apoptosis of human papillomavirus (HPV) positive human cervical cancer cell lines via the nuclear factor (NF)-kB-p53-caspase-3 pathway. The study concluded that curcumin combined with paclitaxel may provide superior therapeutic effects on human cervical cancer.…”

Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features

“…Curcumin has been reported to synergistically enhance the cell growth inhibitory activity of Paclitaxel, a chemotherapeutic, in HPV‐positive human cancer cell lines, as it increased E6/E7 protein inhibition and thereby restored cellular p53 and pRb levels . Using a raft culture technique in which the multilayered and differentiated cell growth of epithelial cells supported the development of HPV in vitro , curcumin alone was able to induce cell death in HPV16 infected CaSki cells and the cleavage products of caspase 9 and 3 (indicators of apoptosis) were found .…”

“…These are just some of the mechanisms elucidated to date as to why therapeutic interventions, while harmful to cancer cells, have failed in achieving an absolute treatment success . Therefore, adjuvant agents that can offer specific cancer toxicity or synergistic effects along with the current nonspecific, noxious chemo‐agents, are desperately needed .…”