8.4 Prostate Cancer

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Although nonmetastatic prostate cancer now has a cure rate approaching 100%, prostate cancer is still the second leading cause of cancer death in men. In vitro studies suggest several cannabis compounds that may help.

Prostate cancer cells are classified as androgen-dependent if they need androgen and androgen-independent if they don't. Androgen-dependent cancers are often treated with androgen deprivation therapy, which works if they don't become androgen independent[pro2]. 

Killing Cancer Cells

CBD has induced apoptosis in vitro and reduced the size of androgen-dependent tumors in animal studies[cyt-cbd1][cyt-cbd2]. THC is known to induce apoptosis of androgen-dependent prostate cancer cells[cyt-thc].

BCPO (β-caryophyllene oxide) has induced apoptosis on several prostate cancer lines[cyt-bcpo] and is synergistic with the chemo drug doxorubicin[cyt-bcpo2]. α-Humulene is cytotoxic against androgen-dependent prostate cancer cells[cyt-hum][cyt-hum2].

The flavonoid apigenin promotes apoptosis[cyt-api1][cyt-api2][cyt-api3][cyt-api4] and is synergistic with the chemo drug cisplatin[cyt-api5].

Stopping Cell Replication

Menthol promotes cell cycle arrest in androgen-independent prostate cancer cells[repl-menth]. The flavonoid apigenin accomplishes cell-cycle arrest and apoptosis in prostate cancer cells — both androgen-dependent[repl-api][repl-api3] and androgen-independent cells[repl-api2].

Inhibiting Invasion and Metastasis

BCPO inhibits invasion in prostate cancer cells[inv-bcpo]. Menthol inhibits motility of androgen-independent cancer cells[inv-menth].

Suppressing Inflammatory Cytokines

Patients with elevated levels of TNF-α and IL-1β have a poor prognosis[Rodríguez_Berriguete_2013]. Elevated TGF-β is associated with angiogenesis, metastasis, and poor clinical outcome[Wikström_1998]. IL-6 promotes prostate cancer[Rojas_2011].

CBD lowers IL-6 and IL-8 in several prostate cancer cell lines[cyt-il6]. See Taming Inflammatory Cytokines for general ideas on lowering cytokines.

Controlling Gene Expression

BCPO lowers gene expression in order to inhibit angiogenesis as well as cell proliferation and metastasis[gene-bcpo].

References

Rojas_2011. IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR. Extended abstract. Rojas A, Liu G, Coleman I, et al. Oncogene. 2011 January 24.

pro2. Hormone therapy can make prostate cancer worse, study finds. Exposition. Cedars-Sinai Medical Center (about). Medical Xpress. Published 2018 September 5.

cyt-cbd1. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms [xenograft study]. Full text. Luciano De Petrocellis (Istituto di Cibernetica, Italy), Alessia Ligresti, Aniello Schiano Moriello, et al. British journal of pharmacology. Published 2013 January.

cyt-il6. In Vitro Anticancer Activity of Plant-Derived Cannabidiol on Prostate Cancer Cell Lines. Abstract. Manju Sharma (bio), James B Hudson, Hans Adomat, et al. Scientific Research. Published 2014 July.

cyt-cbd2. Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent. Full text. Sandeep Sreevalsan (bio), Sonia Joseph, Indira Jutooru, et al. Anticancer Research. Published 2011 November.

cyt-thc. Δ9-Tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. Full text. Lidia Ruiz, Alberto Miguel, Inés Dı́az-Laviada. FEBS Letters. Published 1999 September 21.

cyt-api1. Apigenin drives the production of reactive oxygen species and initiates a mitochondrial mediated cell death pathway in prostate epithelial cells. Abstract. Colm Morrissey (bio), Amanda O'Neill, Barbara Spengler, et al. The Prostate. Published 2005 May 1.

cyt-api2. Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Abstract. Sanjay Gupta, Farrukh Afaq, Hasan Mukhtar. Biochemical and Biophysical Research Communications. Published 2001 October 5.

cyt-api3. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Full text. Sanjay Gupta, Farrukh Afaq, Hasan Mukhtar. Oncogene. Published 2002 May 23.

cyt-api4. Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation. Full text. Sanjeev Shukla (bio), Sanjay Gupta. Free radical biology & medicine. Published 2008 May 15.

cyt-api5. The natural flavonoid apigenin sensitizes human CD44 + prostate cancer stem cells to cisplatin therapy. Full text. Suat Erdogan (Trakya University, Turkey), Kader Turkekul, Rıza Serttas, Zeynep Erdogan. Biomedicine & pharmicotherapy. Published 2017 April.

cyt-bcpo. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Abstract. Kyung-Ran Park (Kyung Hee University), Dongwoo Nam, Hyung-Mun Yun, et al. Cancer Letters. Published 2011 December 22.

cyt-bcpo2. The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells. Full text. Martin Ambrož (Charles University in Prague), Iva Boušová, Adam Skarka, et al. Molecules. Published 2015 August 21.

cyt-hum. In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines. Abstract. Rosa Tundis (University of Calabria), Monica R Loizzo, Marco Bonesi, et al. Natural Product Research. Published 2009.

cyt-hum2. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. Abstract. Jean Legault (UMR-Institut National de la Santé et de la Recherche Médicale), Wivecke Dahl, Eric Debiton, et al. Planta Medica. Published 2003 May.

repl-menth. Menthol inhibits the proliferation and motility of prostate cancer DU145 cells. Full text, abstract. Yongzhi Wang (Wuhan University), Xinghuan Wang (bio), Zhonghua Yang, et al. Pathology oncology research. 2012 March 22.

repl-api. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retin oblastoma dephosphorylation in human prostate cancer cells. Abstract. Sanjeev Shukla (bio), Sanjay Gupta. Cell cycle. Published 2007 May 15.

repl-api3. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Abstract. Sanjay Gupta, Farrukh Afaq, Hasan Mukhtar. Oncogene. 2002 May 23.

repl-api2. Molecular mechanisms for apigenin-induced cell-cycle arrest and apop tosis of hormone refractory human prostate carcinoma DU145 cells. Abstract. Sanjeev Shukla (bio), Sanjay Gupta. Molecular Carcinogenesis. 2004 January 23.

inv-menth. Menthol inhibits the proliferation and motility of prostate cancer DU145 cells. Full text, abstract. Yongzhi Wang (Wuhan University), Xinghuan Wang (), Zhonghua Yang, et al. Pathology Oncology Research. 2012 March 22.

inv-bcpo. β-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase. Full text. Chulwon Kim (College of Korean Medicine), Somi K Cho, Shweta Kapoor, et al. Molecular carcinogenesis.  2013 June 13.

gene-bcpo. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Abstract. Kyung-Ran Park (Kyung Hee University) , Dongwoo Nam, Hyung-Mun Yun, et al. Cancer Letters. 2011 August 26.

Rodríguez_Berriguete_2013. Clinical significance of both tumor and stromal expression of components of the IL-1 and TNF-α signaling pathways in prostate cancer. Abstract.
Rodríguez-Berriguete G, Sánchez-Espiridión B, Cansino J R, et al. Cytokine. Online 2013 September 21.

Wikström_1998. Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Abstract. Wikström P, Stattin P, Franck-Lissbrant I, et al. Prostate. Published 1998 September.