Forty-seven ovarian cancer cases in which 20 were previously treated with cisplatin (cisPt) based chemotherapy, were checked for in vitro chemosensitivity using MTT assay. The drugs included in the study were cisPt, adriamycin (ADR), epirubicin (EPR) and etoposide (ETO). The logarithemic concentrations (0.1, 1.0, 10.0 and 100.0 micrograms/ml) of these drugs were used in the MTT assay. The IC50 values for these drugs in the above tumor samples were calculated. The effect of pretreatment with cisPt based chemotherapy on the emergence of drug resistance, expression of p53 protein (detected using immunohistochemical method by employing monoclonal antibody to p53) and intracellular glutathione (GSH) levels was also studied. Our results demonstrated the superiority of EPR in terms of its efficacy as compared to the other drugs used in the study. EPR was effective in both, previously cisPt-exposed and cisPt-unexposed ovarian cancer cases indicating its importance as a second line chemotherapy in the refractory ovarian carcinoma cases. Pre-exposure to cisPt based chemotherapy appears to result in the emergence of cisPt resistance, elevated intracellular GSH levels as well as p53 positivity. A statistically significant correlation was also observed between ADR and EPR resistance and p53 positivity (P < 0.01 and 0.05 respectively).
Background
The anti-cancer activity of phytomolecules present in turmeric or
haridra
(
Curcuma longa
Linn) extracts against cancer has been described in various ‘
in vitro
and
in vivo’
studies.
Objective
In the present study,
in vitro
and
in vivo
anti-cancer and chemo-preventive activity of a new standardized Supercritical Turmeric Oil Extract (SCTOE) NBFR-03 was evaluated in cervical cancer models.
Methods and materials
In vitro
cytotoxicity of this formulation was assessed at 10, 20, 40, and 80 μg/ml concentrations, in three cervical cancer cell lines (HeLa, SiHa, ME180) using Sulforhodamine B assay. The
in vivo
anti-cancer activity was evaluated in two groups of female nude mice; the first one was with tumor xenograft implants and at the same time treatment was started with 96 μl/kg/day p.o. and 192 μl/kg/day p.o. NBFR-03 for three months. The second group was kept as chemoprevention group where mice were pre-treated with the formulation (96 μl/kg/day p.o.) for two weeks and injected with cancer cell suspension with continued treatment for three months.
Results
No cytotoxicity was seen in any cell line with the extract when compared to positive control (Adriamycin 10 μg/ml). In mice the first treatment group with tumor xenograft implants did not show any significant anti-tumor activity but showed a trend where higher dose group had smaller tumor volumes as compared to lower dose group and controls (p = 0.37 and p = 0.34 respectively). The chemopreventive group with pre-treated mice also showed smaller tumor size as compared to controls (p = 0.163).
Conclusion
NBFR-03 turmeric oil extract showed a promising trend in mice pre-treated with NBFR-03. There is a scope for further studying the potential of this extract as complementary therapy and as a chemopreventive.
Thirty cases of previously untreated advanced larynx carcinoma were checked for in vitro chemosensitivity and presence of the resistance markers viz. P-glycoprotein (P-gp) glutathione-S-transferase-pi (GST-pi) and protein kinase C (PKC) overexpression. The cytotoxicity testing was done using MTT assay and the resistance markers were checked by immunohistochemical methods using monoclonal antibodies. The drug combinations employed in MIT assay were 5FU* + MTX*, 5FU + cisPt*, 5FU + Mito*, cisPt + Mito and MTX + Mito (*5FU = 5Fluorouracil, MTX-methotrexate, cisPt-cisplatin and Mito = mitomycin C). No statistically significant correlation was observed between resistance to the above drug combinations and presence of the resistance markers under consideration. A statistically significant correlation was observed between node positivity and expression of resistance markers which indicates that presence of one or more of these markers in these tumors may be considered as a negative prognosis marker. CisPt-Mito was found to be the most effective drug combination in vitro, in the cases studied.
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