Transforming growth factor-beta3 protection of epithelial cells from cycle-selective chemotherapy in vitro.

Abstract:

:The transforming growth factor-beta (TGF-beta) family of regulatory growth factors can reversibly arrest cell division in the G1 phase of the cell cycle. Previously, TGF-beta3 was shown to protect epithelial cells and hematopoietic cells from cytotoxic damage in vitro and in vivo, and to reduce the severity and duration of oral mucositis induced by 5-fluorouracil (5-FU) in vivo. In the present study, we tested whether TGF-beta3 can protect epithelial cells from a range of chemotherapy drugs with differing mechanisms of action, using the CCL64 cell line as a model system. We report that preincubation of cells with TGF-beta3 for 24 hr resulted in enhanced clonogenicity following exposure to vinblastine, vincristine, etoposide, taxol, ara-C, methotrexate, or 5-FU. Protection was measured in colony-forming assays, which demonstrated that the protected cells could re-enter the cell cycle and undergo multiple rounds of cell division. At high cytotoxic drug concentrations, absolute colony counts were increased for the cultures prearrested by TGF-beta3, as compared with the proliferating control cultures. The effects of TGF-beta3 were reduced for cisplatin and doxorubicin, drugs that are toxic to cells throughout the cell cycle. Thus, TGF-beta3 can effectively reduce the cytotoxicity of anticancer drugs that act predominantly in S or M phase of the cell cycle.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

McCormack ES,Borzillo GV,Ambrosino C,Mak G,Hamablet L,Qu GY,Haley JD

doi

10.1016/s0006-2952(97)00094-4

subject

Has Abstract

pub_date

1997-04-25 00:00:00

pages

1149-59

issue

8

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(97)00094-4

journal_volume

53

pub_type

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