title: Baccatin III, a precursor for the semisynthesis of paclitaxel, inhibits the accumulation and suppressive activity of myeloid-derived suppressor cells in tumor-bearing mice.
abstract: Myeloid-derived suppressor cells (MDSCs) mediate tumor-associated immune suppression in both cancer patients and tumor-bearing animals. Reduction or elimination of MDSCs reduces the rate of tumor progression and improves cancer therapies that employ mechanisms of immunity. Here we show that baccatin III, which is the precursor for the semisynthesis of paclitaxel, exerts anti-tumor immunomodulatory activity in very low doses (0.05-0.5mg/kg), although it is regarded as an inactive derivative of paclitaxel. Oral administration of baccatin III significantly reduced the growth of tumors induced by engrafting BALB/c mice with either 4 T1 mammary carcinoma or CT26 colon cancer cells. Baccatin III (0.5mg/kg) did not exert anti-tumor activity in athymic nude mice. Baccatin III decreased the accumulation of MDSCs in the spleens of the tumor-bearing mice. Furthermore, MDSCs isolated from baccatin III-treated mice, compared with those isolated from vehicle-treated mice, had a significantly reduced suppressive effect on T cells treated with the anti-CD3 and anti-CD28 monoclonal antibodies. Moreover, these cells produced significantly reduced amounts of reactive oxygen species and nitric oxide. These results suggest that baccatin III reduced tumor progression by inhibiting the accumulation and suppressive function of MDSCs.
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Young-Hee
authors: YH
authors: Lee
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Young-Ran
authors: YR
authors: Lee
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Chan-Su
authors: CS
authors: Park
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Sun-A
authors: SA
authors: Im
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Sukgil
authors: S
authors: Song
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Jin Tae
authors: JT
authors: Hong
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
authors: Bang Yeon
authors: BY
authors: Whang
authors: College of Pharmacy, SahmYook University, Seoul 139-742, South Korea.
authors: Kyungjae
authors: K
authors: Kim
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea. Electronic address: cklee@chungbuk.ac.kr.
authors: Chong-Kil
authors: CK
authors: Lee
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D043823:Taxoids; C073950:baccatin III; D017239:Paclitaxel
keywords: Baccatin III; Colon cancer; Mammary carcinoma; Myeloid-derived suppressor cell