ginsenoside-rg5 and Uterine-Cervical-Neoplasms

In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensitize cells to paclitaxel. Ginsenoside Rg5 (GRg5) may act as a chemosensitizer by reversing multidrug resistance. The present study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). MTT assay was carried out to assess whether GRg5 can potentiate the cytotoxic effect of PTX in PTX- resistant HeLa cells; using flow cytometry-based annexin V-FITC assay, cellular apoptosis was analyzed; the rate of expression of the cell cycle, apoptosis and major cell-survival-signaling-related genes and its proteins were examined using RT-PCR and Western blotting technique. We found increased mRNA expression of Bak, Bax, Bid, and PUMA genes, whereas the mRNA expression of Bcl2, Bcl-XL, c-IAP-1, and MCL-1 were low; GRg5 combination triggered the efficacy of paclitaxel, which led to increased expression of Bax with an enhanced caspase-9/-3 activation, and apoptosis. Moreover, the study supports GRg5 as an inhibitor of two key signaling proteins, Akt and NF-κB, by which GRg5 augments the susceptibility of cervical cancer cells to PTX chemotherapy. GRg5 drastically potentiated the antiproliferative and pro-apoptotic activity of paclitaxel in PTX-resistant human cervical cancer cells in a synergistic mode. Moreover, in the clinical context, combining paclitaxel with GRg5 may prove to be a new approach for enhancing the efficacy of the paclitaxel.

Topics: bcl-2-Associated X Protein; Cell Line, Tumor; Female; Ginsenosides; HeLa Cells; Humans; Paclitaxel; RNA, Messenger; Uterine Cervical Neoplasms

Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside‑Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside‑Rg5 had any marked cytotoxic, apoptotic or DNA‑damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT‑3) were used to investigate the cytotoxicity of ginsenoside‑Rg5 using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside‑Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of γH2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside‑Rg5 treatment compared with the C‑33A, HT‑3 and Me180 cells. As expected, ginsenoside‑Rg5 induced significant concentration‑ and time‑dependent increases in apoptosis. In addition, ginsenoside‑Rg5 induced significant concentration‑dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of γH2AX‑positive HeLa and MS751 cells also revealed that ginsenoside‑Rg5 caused DNA double‑strands to break in a concentration‑dependent manner. In conclusion, ginsenoside‑Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Survival; Comet Assay; DNA Damage; DNA Fragmentation; Female; Ginsenosides; HeLa Cells; Humans; Panax; Uterine Cervical Neoplasms