Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis

Anju Preet, Zahida Qamri, Mohd W. Nasser, Anil Prasad, Konstantin Shilo, Xianghong Zou, Jerome E. Groopman, Ramesh K. Ganju

Research output: Contribution to journalArticle

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Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC. We observed expression of CB1 (24%) and CB2 (55%) in NSCLC patients. Furthermore, we have shown that the treatment of NSCLC cell lines (A549 and SW-1573) with CB1/CB2- and CB2-specific agonists Win55,212-2 and JWH-015, respectively, significantly attenuated random as well as growth factor-directed in vitro chemotaxis and chemoinvasion in these cells. We also observed significant reduction in focal adhesion complex, which plays an important role in migration, upon treatment with both JWH-015 and Win55,212-2. In addition, pretreatment with CB1/CB2 selective antagonists, AM251 and AM630, prior to JWH-015 and Win55,212-2 treatments, attenuated the agonist-mediated inhibition of in vitro chemotaxis and chemoinvasion. In addition, both CB1 and CB2 agonists Win55,212-2 and JWH-133, respectively, significantly inhibited in vivo tumor growth and lung metastasis (∼50%). These effects were receptor mediated, as pretreatment with CB1/CB2 antagonists abrogated CB1/CB2 agonist-mediated effects on tumor growth and metastasis. Reduced proliferation and vascularization, along with increased apoptosis, were observed in tumors obtained from animals treated with JWH-133 and Win55,212-2. Upon further elucidation into the molecular mechanism, we observed that both CB1 and CB2 agonists inhibited phosphorylation of AKT, a key signaling molecule controlling cell survival, migration, and apoptosis, and reduced matrix metalloproteinase 9 expression and activity. These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalCancer Prevention Research
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2011

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Cannabinoid Receptor CB2
Cannabinoid Receptor CB1
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Growth
Chemotaxis
Therapeutics
Neoplasms
Apoptosis
Focal Adhesions
Matrix Metalloproteinase 9
Inhibition (Psychology)
Cell Movement
Cause of Death
Cell Survival
Intercellular Signaling Peptides and Proteins
Phosphorylation
Lung

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. / Preet, Anju; Qamri, Zahida; Nasser, Mohd W.; Prasad, Anil; Shilo, Konstantin; Zou, Xianghong; Groopman, Jerome E.; Ganju, Ramesh K.

In: Cancer Prevention Research, Vol. 4, No. 1, 01.01.2011, p. 65-75.

Research output: Contribution to journalArticle

Preet, Anju ; Qamri, Zahida ; Nasser, Mohd W. ; Prasad, Anil ; Shilo, Konstantin ; Zou, Xianghong ; Groopman, Jerome E. ; Ganju, Ramesh K. / Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 1. pp. 65-75.
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