AI Article Synopsis

  • Two human thyroid tumor cell lines, hPTC and hAG, were created from patients with papillary thyroid carcinoma and adenomatous goiter, respectively, both of which responded to TSH stimulation by increasing cAMP levels.
  • The effectiveness of several anticancer drugs was tested on hPTC cells, with doxorubicin showing the lowest ED50 and significant effects on cellular DNA content that persisted even after a short exposure, unlike other drugs that displayed time-dependent effects.
  • The sensitivity of hPTC to doxorubicin was compared to hAG, revealing that hPTC had a much lower ED50, and the study also examined how antioxidants like glutathione affected the drugs' potency against the tumor cells.

Article Abstract

We established two human thyroid tumor cell lines. One cell line (hPTC) was established from the tissue of a papillary thyroid carcinoma surgically excised from a 27-year-old female patient. The other cell line (hAG) was established from the tissue of an adenomatous goiter excised from a 59-year old female patient. Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. hPTC and hAG continued to divide as a monolayer in a tissue culture for three years and two years, respectively. We assessed the efficacy of anticancer drugs (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 times that of the ED50. The clinical blood concentration divided by ED50 for the other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed time-independent effects since a 2-hour exposure of ADR to the hPTC cells resulted in the significant reduction of the cellular DNA content of the live cells even after 48 hours. The effects of the other anticancer drugs were time-dependent. We then studied the difference of the effects of ADR on hPTC and hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG (0.460 mu g/ml). Since free radical formation is one of the major anticancer mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH catches up with free radicals in the extracellular fluid. NAC promotes production of GSH in the cytoplasm, but BSO interferes with the production of GSH in the cytoplasm. alpha-toco catches up with free radicals on the plasma membrane. GSH and alpha-toco did not effect ED50 for hPTC and hAG. However, NAC increased ED50 for hPTC and hAG, and BSO reduced ED50 for hPTC and hAG. The effects of NAC and BSO on ED50 for hPTC were greater than those for hAG.(ABSTRACT TRUNCATED AT 400 WORDS)

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrine1927.71.1_73DOI Listing

Publication Analysis

Top Keywords

hptc hag
28
anticancer drugs
20
ed50 hptc
20
hptc
13
free radicals
12
hag
9
effects anticancer
8
human thyroid
8
cell lines
8
established tissue
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!