Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy.
The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean +/- SEM, v/v) were 0.40 +/- 0.02, 0.39 +/- 0.02, 0.94 +/- 0.05, and 0.65 +/- 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 +/- 0.27, 1.35 +/- 0.20, and 0.85 +/- 0.18 cm(3) after injection with 10, 30, or 50 microL per 72 h (six times), respectively, as opposed to 3.88 +/- 0.50 cm(3) for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 +/- 4, 18 +/- 4, and 8 +/- 3%, respectively, while the control animals showed 75 +/- 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.
Ait M'barek
L
L
Laboratory of Immunology, Biochemistry and Molecular Biology, Natural Substances, Cellular and Molecular Immuno-pharmacology Group, Faculty of Sciences and Technologies, University Cadi-Ayyad, Béni-Mellal, Morocco.
Ait Mouse
H
H
Jaâfari
A
A
Aboufatima
R
R
Benharref
A
A
Kamal
M
M
Bénard
J
J
El Abbadi
N
N
Bensalah
M
M
Gamouh
A
A
Chait
A
A
Dalal
A
A
Zyad
A
A
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology*; D046930:Thymus Plant / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D010938:Plant Oils