Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents Journal Article


Authors: Sacks, P. G.; Harris, D.; Chou, T. C.
Article Title: Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents
Abstract: We have previously shown that β‐all trans retinoic acid (RA) inhibits macrocellular growth of a multicellular tumor spheroid model for squamous carcinoma, as measured by spheroid size, but allows for continuing DNA synthesis and cell cycle progression, the two being reconciled by a cell death effect. DNA synthesis in the presence of growth inhibition suggested a rationale for examining combination chemotherapy with RA‐inhibited cells. To this aim, we have extended this observation to a series of 8 squamous carcinoma cell lines. Cells were treated with 1 μM RA for 7 days and cell growth parameters monitored. Although growth inhibition ranged from 0% (A431) to approx. 80% (MDA 886Ln), [3H]‐thymidine incorporation (cpm/μg protein) and percent S‐phase (by flow cytometry) in 7‐day RA‐treated cells was equal or higher than in their control vehicle‐treated cells in 7/8 SCC cell lines. Thus RA‐induced growth inhibition is not just cytostasis. Combination therapy was examined with MDA 886Ln, MDA 686Ln, 1483 and A431 cells pre‐treated for 7 days with 1 μM RA followed by cisplatin or 5‐fluorouracil treatment. An increased effectiveness for the combination was shown using 5‐day tetrazolium dye (MTT) growth assays when cells were growth‐inhibited by RA. Computerized analysis of data using median‐effect and isobologram techniques indicated that the interaction of RA with these chemotherapeutic agents was synergistic. With squamous carcinoma, RA treatment inhibits growth while allowing for continuing DNA synthesis, and these RA‐treated, growth‐inhibited cells exhibit increased sensitivity to chemotherapeutic agents. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc., A Wiley Company
Keywords: controlled study; human cell; squamous cell carcinoma; carcinoma, squamous cell; cisplatin; fluorouracil; drug potentiation; antineoplastic agents; cell proliferation; cell survival; cell cycle; cell cycle s phase; cell division; cell line; combination chemotherapy; dose-response relationship, drug; tumor cells, cultured; drug therapy, combination; head and neck neoplasms; dna, neoplasm; retinoic acid; s phase; growth inhibition; tretinoin; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: International Journal of Cancer
Volume: 61
Issue: 3
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 1995-05-04
Start Page: 409
End Page: 415
Language: English
DOI: 10.1002/ijc.2910610322
PUBMED: 7729955
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
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MSK Authors
  1. Peter G Sacks
    53 Sacks
  2. Ting-Chao Chou
    318 Chou
  3. Daniel   Harris
    5 Harris