Role of triptolide as an adjunct chemotherapy for ovarian cancer.
BACKGROUND
Triptolide (TPL) has been identified as the active component of the Tripterygium wilfordii hook F plant and demonstrated to possess antitumor properties and induce apoptosis in a variety of tumor cell lines. Since TPL actions are associated with changes in the activities of both p53 and NF kappaB, which are implicated in the chemoresistance of ovarian cancer, the ability of TPL to be a potential chemotherapeutic for ovarian cancer was considered.


METHODS
TPL actions on human ovarian cancer cells were investigated in vitro and in vivo with a nude mouse model to monitor tumor burden both in the absence or presence of other chemotherapy agents.


RESULTS
TPL was effective as a single agent in inducing apoptosis of ovarian cancer cells in vitro, but not in vivo. TPL enhanced the cytotoxicity of carboplatin in culture and enhanced carboplatin-mediated reduction of tumor burden in nude mice inoculated with human ovarian cancer cells. Previously, a phosphatidylinositol 3-kinase (PI3 kinase) inhibitor was found to enhance carboplatin actions on ovarian cancer. Interestingly, the combined treatment of TPL, PI3 kinase inhibitor LY294002 and carboplatin was found to dramatically reduce ovarian tumor progression and burden in nude mice.


CONCLUSIONS
In 44% of the animals tested the combined treatment caused complete regression of ovarian cancer. Combined observations indicate TPL may be an effective adjunct chemotherapy for ovarian cancer.
Westfall
Suzanne D
SD
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4231, USA.
Nilsson
Eric E
EE
Skinner
Michael K
MK
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D002867:Chromones / Q000008:administration & dosage; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012074:Remission Induction; D029757:Tripterygium / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects*
D018906:Antineoplastic Agents, Alkylating; D002867:Chromones; D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D009025:Morpholines; D010616:Phenanthrenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; C001899:triptolide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016190:Carboplatin