92195-114

Antitumor effect of Chinese herb oridonin on human non-small cell lung cancer (NSCLC).

Subcategory: 
Category: 
Developmental Therapeutics - Experimental Therapeutics
Session Type and Session Title: 
This abstract will not be presented at the 2012 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 

e13526

Citation: 

J Clin Oncol 30, 2012 (suppl; abstr e13526)

Author(s): 

Siyu Chen, Wei Tian, Ai-Hong Ma, Sonal Desai, Krysteena Tolentino, Yantong Guo, Tianhong Li; Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Hematology/Oncology, University of California Davis Cancer Center, Sacramento, CA


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Oridonin, a diterpenoid purified from the Chinese herb Rabdosia rubescens, has anti-inflammatory and potentially anti-tumor property. We aimed to study the antitumor effect of oridonin on a panel of human non-small cell lung cancer (NSCLC) cell lines. Methods: Human NSCLC cell lines with a wild-type EGFR gene and a RAS gene mutation were treated with escalating dose concentration of oridonin (from 2.5 to 50 µM). Antitumor effect was measured by 72-hr growth inhibition by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell morphology was observed under microscope. Ongoing experiments will identify potential drug target(s) by assessing changes in global gene expression. Results: Oridonin exhibited a dose-dependent and time-dependent cytotoxic effect on a panel of NSCLC cell lines. Table 1 summarizes the molecular and histological features of these NSCLC cells, and their cytotoxicity to oridinin, erlotinib and pemetrexed. In those NSCLC cells that were sensitive to oridonin, morphological changes were consistent with autophagy and apoptosis. Potential drug targets will be verified by RT-PCR and immunoblotting. Conclusions: Oridonin exerts a distinct cytotoxicity that is independent of the sensitivity of NSCLC cells to erlotinib or pemetrexed. Further mechanistic and animal studies are warranted to understand its anti-tumor property and toxicity profile in preclinical evaluation.
Characterization of NSCLC cell lines used in the study.
Cell line Cell type EGFR gene RAS mutation p53 mutation Erlotinib IC50
(µM, mean±SD)
Pemetrexed IC50
(µM, mean±SD)
Oridonin IC50
(µM, mean±SD)
H358 bronchoalveolar Wild-type KRAS G12C Homozygous
deletion
1.50 ± 0.16 0.24 ± 0.04 31.45±7.60
R#2 adenocarcinoma Wild-type NRAS Q61K Wild-type >20 0.34 ± 0.06 24.76±3.17
H23 adenocarcinoma Wild-type KRAS G12C M246I >20 0.46 ± 0.08 25.72±1.17
A549 adenocarcinoma Wild-type KRAS G12S Wild-type >20 0.35 ± 0.06 79.48±28.20