Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model.
Coriander, used as a common food seasoning, contains linalool as the main constituent of its essential oil. In this study, we tested the effect of linalool vis-à-vis that of a conventional chemotherapeutic drug, cyclophosphamide, against solid S-180 tumor-bearing Swiss albino mice. Tumor volume, cell count, cell cycle phase distribution, apoptosis, and proliferation markers indicate that linalool has potent antitumor activity. In vitro and in vivo data suggest that induction of oxidative stress might be responsible for the anticancer effect of linalool. However, interestingly, unlike cyclophosphamide, linalool did not induce myelosuppression or hepatotoxicity in mice as evident from bone marrow cell count, status of hepatic oxidative stress/antioxidant enzymes, and histopathology. Thus, linalool exerted prooxidant effect in tumor tissue and an antioxidant effect in liver. This is also supported by the expression of Nrf-2 and p21, which are considered to be important players in response to oxidative stress. Moreover, administration of linalool modulated the proliferation of spleen cells in tumor-bearing mice challenged with lipopolysaccharide. Finally, the detection of linalool in sera and tumor tissues by HPLC confirmed its bioavailability. In conclusion, linalool showed differential cytotoxicity towards tumor and normal cells in contrast to cyclophosphamide, which is uniformly toxic to both.
a Department of Zoology , West Bengal State University , West Bengal , India.
Samarjit
S
Jana
Kartick
K
Patra
Shehnaz
S
Sarkar
Jagannath
J
Jana
Gopeswar
G
Mukherjee
Shamee
S
Bhattacharjee
Deba Prasad
DP
Mandal
D000080462:Acyclic Monoterpenes; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012510:Sarcoma 180 / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; D000975:Antioxidants; C494827:Bax protein, mouse; D008070:Lipopolysaccharides; D039821:Monoterpenes; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003520:Cyclophosphamide; C018584:linalool; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione