Cannabidiolic acid, a major cannabinoid in fiber-type cannabis,an inhibitor of MDA-MB-231 breast cancer cell migration

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Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration

• Shuso Takeda^a,
• Shunsuke Okajima^a,
• Hiroko Miyoshi^a,
• Kazutaka Yoshida^a,
• Yoshiko Okamoto^a,
• Tomoko Okada^b,
• Toshiaki Amamoto^c,
• Kazuhito Watanabe^d,
• Curtis J. Omiecinski^e,
• Hironori Aramaki^{a, ,}

• ^a Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan
• ^b Signaling Molecules Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8566, Japan
• ^c NEUES Corporation, Yaesu Center Building 3F, 1-6-6 Yaesu, Chuo-ku, Tokyo 103-0028, Japan
• ^d Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan
• ^e Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802, United States

• http://dx.doi.org/10.1016/j.toxlet.2012.08.029, How to Cite or Link Using DOI

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Abstract

Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, has been reported to possess diverse biological activities, including anti-proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies have investigated whether CBDA itself is biologically active. Results of the current investigation revealed that CBDA inhibits migration of the highly invasive MDA-MB-231 human breast cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA. It is established that activation of the RhoA signaling pathway leads to inhibition of the mobility of various cancer cells, including MDA-MB-231 cells. The data presented in this report suggest for the first time that as an active component in the cannabis plant, CBDA offers potential therapeutic modality in the abrogation of cancer cell migration, including aggressive breast cancers.

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Highlights

► Cannabidiolic acid (CBDA) exists as a major component in the fiber-type cannabis. ► CBDA is identified as an “active component”. ► CBDA is an inhibitor of highly aggressive human breast cancer cell migration. ► The mechanism responsible for the effects of CBDA involves activation of RhoA. ► RhoA is an inhibitor of cancer cell mobility.

Abbreviations

• CBDA, cannabidiolic acid;
• CBD, cannabidiol;
• COX-2, cyclooxygenase-2;
• PKA, cAMP-dependent protein kinase;
• Δ⁹-THC, Δ⁹-tetrahydrocannabinol