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Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase.
Toxicology. 2009 May 02; 259(1-2):25-32.T

Abstract

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17beta-estradiol (E(2)), the interaction of Delta(9)-THC and E(2) in MCF-7 cell growth is not fully clarified so far. In the present study, by using E(2)-sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Delta(9)-THC-mediated MCF-7 cell proliferation. It was shown that Delta(9)-THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Delta(9)-THC was not stimulated by PGE(2), and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE(2), suggesting that there is a disconnection between COX-2 (PGE(2)) and aromatase in Delta(9)-THC-mediated MCF-7 cell proliferation. On the other hand, Delta(9)-THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Delta(9)-THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E(2), it is suggested that (1) the growth stimulatory effects of Delta(9)-THC are mediated by the product(s) of COX-2 except for PGE(2), (2) the action of Delta(9)-THC is modulated by E(2), and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Delta(9)-THC.

Authors+Show Affiliations

Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19428940

Citation

Takeda, Shuso, et al. "Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 Breast Cancer Cell Growth By Cyclooxygenase and Aromatase." Toxicology, vol. 259, no. 1-2, 2009, pp. 25-32.
Takeda S, Yamamoto I, Watanabe K. Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase. Toxicology. 2009;259(1-2):25-32.
Takeda, S., Yamamoto, I., & Watanabe, K. (2009). Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase. Toxicology, 259(1-2), 25-32. https://doi.org/10.1016/j.tox.2009.01.024
Takeda S, Yamamoto I, Watanabe K. Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 Breast Cancer Cell Growth By Cyclooxygenase and Aromatase. Toxicology. 2009 May 2;259(1-2):25-32. PubMed PMID: 19428940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase. AU - Takeda,Shuso, AU - Yamamoto,Ikuo, AU - Watanabe,Kazuhito, Y1 - 2009/02/04/ PY - 2008/11/28/received PY - 2009/01/26/revised PY - 2009/01/26/accepted PY - 2009/5/12/entrez PY - 2009/5/12/pubmed PY - 2009/6/3/medline SP - 25 EP - 32 JF - Toxicology JO - Toxicology VL - 259 IS - 1-2 N2 - Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17beta-estradiol (E(2)), the interaction of Delta(9)-THC and E(2) in MCF-7 cell growth is not fully clarified so far. In the present study, by using E(2)-sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Delta(9)-THC-mediated MCF-7 cell proliferation. It was shown that Delta(9)-THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Delta(9)-THC was not stimulated by PGE(2), and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE(2), suggesting that there is a disconnection between COX-2 (PGE(2)) and aromatase in Delta(9)-THC-mediated MCF-7 cell proliferation. On the other hand, Delta(9)-THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Delta(9)-THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E(2), it is suggested that (1) the growth stimulatory effects of Delta(9)-THC are mediated by the product(s) of COX-2 except for PGE(2), (2) the action of Delta(9)-THC is modulated by E(2), and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Delta(9)-THC. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/19428940/Modulation_of_Delta9_tetrahydrocannabinol_induced_MCF_7_breast_cancer_cell_growth_by_cyclooxygenase_and_aromatase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(09)00077-8 DB - PRIME DP - Unbound Medicine ER -