rhinacanthin-c and Mouth-Neoplasms

The search for effective herbal medicines for complementary treatments is on the rise due to the high incidence of recurrence and mortality rate in human oral cancer. Rhinacanthus nasutus KURZ., an annual herb found mostly in Southeast Asia including Thailand, has been wildly used as a traditional folk medicine for the treatment of several diseases including cancer. However, the anti-cancer effect of Rhinacanthin-C (Rh-C) as a major naphthoquinone compound found in R. nasutus and the underlying mechanism of its action on human oral cancer cells remain unknown.. To investigate the anti-cancer mechanism of Rh-C extracted from R. nasutus in human oral cancer cells.. The anti-proliferative effect of Rh-C on human oral squamous cell carcinoma (HSC4) was determined and compared to normal oral cells (human gingival fibroblasts, HGF, and normal oral keratinocytes, NOK) using the SRB colorimetric method. The molecular mechanism of Rh-C was explored using flow cytometry, colorimetric assay, in vitro human topoisomerase II assay, and Western blotting.. Rh-C displayed a time- and concentration-dependent growth inhibition on HSC4 and was much less effective on both tested normal oral cells. Rh-C inhibited Akt phosphorylation whereas over-activated p38 MAPK phosphorylation in HSC4 but not in HGF. Rh-C also inhibited topoisomerase II activity. As a result, the cell cycle was arrested in S-phase as the expression of CDK1/2 and Cyclin A2 was decreased. Eventually, the induction of HSC4 cell apoptosis was mediated by increased caspase 3 activity.. Rh-C isolated from R. nasutus possesses anti-cancer properties on human oral cancer cells by causing the S arrest and the apoptotic induction via modulating Akt/p38 signaling pathways. The results provide molecular bases for further developing Rh-C as a potential drug candidate or a complementary treatment for oral cancer.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Humans; Mouth Neoplasms; Naphthoquinones; Proto-Oncogene Proteins c-akt; Signal Transduction

To investigate the effects of rhinacanthin-C (Rh-C), 5-FU, and etoposide on growth inhibition, as well as the effects of a combination of these inhibitors on the oral cell lines SCC9 and HSC4.. Cancer cell growth inhibition and inhibition combination were determined using the SRB assay. Cell viability and early apoptosis were determined using flow cytometry on cells stained with Annexin 5 and PI. Western blotting was performed to study the molecular mechanism of these inhibitors on oral cancer cells.. The results showed that etoposide, 5-FU, and Rh-C exhibited more potent anti-proliferative effects on HSC4 cells compared to SCC9 cells in a time- and concentration-dependent manner. The combination of Rh-C and 5-FU was more effective in inhibiting cell growth than the drugs used alone. The combination of 5-FU and Rh-C resulted in a decrease in live HSC4 cells, with the highest percentage of cell death observed at a ratio of 40:6 μM. Furthermore, the combination of 5-FU and Rh-C reduced P-Akt levels leading to a decrease in cell survival.. HSC4 cells were found to be more sensitive to the inhibitory effect of these drugs compared to SCC9 cells. These findings suggest that the use of Rh-C as a complementary therapy with 5-FU may have the potential for the treatment of oral cancer. the underlying mechanisms responsible for this difference in sensitivity between the two cell lines need to be further investigated.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Etoposide; Fluorouracil; Humans; Mouth Neoplasms