Background: Cholangiocarcinoma (CCA)is the primary type of bile duct
cancer with high morbidity and mortality, particularly in patients with
advanced stages. Numerous studies have been carried out in efforts to discover
effective cancer chemotherapeutic agents from plant sources with low toxicity.
Treatment of CCA remains unsatisfactory due to the lack of sensitive and
specific diagnostic tools for early detection and effective chemotherapeutics.
Purpose: The primary purpose of this study is to investigate
cytotoxic interactions between the three major constituents of the rhizomes of
Atractylodeslancea (Thunb)DC., i.e., β-eudesmol (BE), atractylodin (AT), and
hinesol (HS) against CCA cell line.
Methods: The bioactive constituents of AL rhizome under
investigation, ie, BE, AT, HS, and 5-FU were purchased from Wako (Wako Ltd.,
Osaka, Japan). Cytotoxic activities against the human CCA cells CL-6 of the
dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were
evaluated using the assay. The cytotoxic interaction of each dual combination
was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using
isobologram analysis. The fractional inhibitory concentration index of each
combination pair (representing combination scores) and the sum FIC of five
distinctive ratios were calculated as the ratio of IC50 of the combination and
that of each compound alone. For triple combination, the concentration ratio
used in the experiment was 1:1.5:2.5(BE:AT:HS), and analysis of the interaction
was performed using polygonogram analysis at the IC50 and IC90 concentrations
(concentration that inhibits cell growth by 50% and 90%, respectively).
Results: The study was the first that confirmed the cytotoxic
synergistic interaction of the three major compounds from AL rhizome on the
human CCA cell line CL-6. The BE:AT combination produced the additive effect
with a sum FIC (fractional inhibitory concentration) of 0.967±0.02 (mean±SD).
The BE:HS and AT:HS combinations produced a synergistic effect with sum FICs of
0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds
produced synergistic interaction with CI (combination index) values of
0.519±0.10 and 0.65±0.17 (mean±SD) at the IC50 and IC90 concentration
levels, respectively.
Conclusion: The multi-ingredient characteristics of the plant
extract would be expected to optimize therapy regarding both efficacy
(synergistic anti-CCA activity) and tolerability (buffering effect). Results
obtained would guide further development of AL as a potential anti-CCA
chemotherapeutics concerning the appropriate pharmaceutical dosage form.
Author
(s) Details
Pongsakorn Martviset
Center of Excellence in Molecular Biology and Pharmacology of Malaria and
Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat
University, Pathumthani 12121, Thailand and Faculty of Medical Technology,
Rangsit University, Pathumthani 12000, Thailand.
Kesara Na-Bangchang
Center of Excellence in Molecular Biology and Pharmacology of Malaria and
Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University,
Pathumthani 12121, Thailand, Graduate Program in Bioclinical Sciences,
Chulabhorn International College of Medicine, Thammasat University, Pathumthani
12121, Thailand and Drug Discovery and Development Center, Thammasat
University, Pathumthani 12121, Thailand.
Please see the book here:- https://doi.org/10.9734/bpi/crpbs/v3/2408
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