Biomolecules & Therapeutics 2008; 16(2): 87-94  
Cannabidiol Induces Cytotoxicity and Cell Death via Apoptotic Pathway in Cancer Cell Lines
Won Hyung CHOI1*, Hyun Do PARK2, Seung Hwa BAEK3, Jong Phil CHU1, Mae Hwa KANG1 and Yu Jing MI1
1Department of Medical Zoology, College of Medicine, KyungHee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea
2Division of Anatomy & Developmental Biology, Department of Oral Biology, BK21 Project, College of Dentistry, Yonsei University, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752 and
3Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, South Korea
Received: April 10, 2008; Accepted: May 22, 2008; Published online: June 30, 2008.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 μM of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB- 231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 μM concentration.
Keywords: Cannabidiol, Cytotoxicity, LDH release, Caspase, Breast cancer cells

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