In Vitro Anti-Proliferative Activity of Cannabis Extract on Human Cancer Cell Lines
Keywords:delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), Cannabis extract, Anti-proliferative, Human cancer cell
Background: Cannabis is classified as a Schedule 5 substance under the Narcotics Act B.E. 2522. Among with various modulatory effects of cannabinoids on body functions, two major cannabinoids are known to be used as medicines. They are a psychoactive delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). Currently, THC and CBD are advised to be used for treatment of a variety of medical conditions. Such as cell growth inhibition, anti-inflammatory effects and tumor regression. Although, potential benefit can be found in the medical condition above mentioned. The use of cannabis in some disease states such as cancer remain to be clinically evaluated in both efficacy and safety aspects through systematic research before being generalized for routine use.Objective: The purpose of this study to investigate the In vitro effects of cannabis extracts on 10 types of human cancer cell line.Methods: Two cannabis extracts (high THC level and high CBD level) were kept in sterile bottles, in refrigerator, until further use when it was dissolved in DMSO to give a stock solution, filtered and stored at 4 °C. The small percentage of DMSO present in the wells (maximal 0.1%) was found not to affect the experiment. The anti-proliferative activities of cannabis extract on cancer cell lines was determined by MTT assay.Results: To evaluate the anti-proliferative activity of the cannabis extracts on 10 types of cancer cell line (lung cancer, breast cancer, colorectal cancer, gastric cancer, cervical cancer, ovarian cancer, liver cancer, pancreatic cancer, cholangiocarcinoma cancer, lymphoma cancer), the cells were treated with different concentrations of high THC level and high CBD level for 72h and cell viability was determined using MTT assay. The results showed that all of cancer cell lines viability significantly reduced in concentration and time dependent manner following treatment with the extract. The IC50 of the high THC level values ranging from 10.80 ±1.03 to 54.60±1.27 μg/mL, and exhibited very strong activity against RBE with IC50 values of 10.80±1.03 μg/mL. The IC50 of the high CBD level values ranging from 6.00±1.16 to 26.00±1.37 μg/mL, and exhibited very strong activity against NCI-N87 with IC50 values of 6.00±1.16 μg/mL.Conclusions: The results suggest that high THC level and high CBD level is a potent human cancer cells proliferation. Further investigations are needed to elucidate the mechanism of anticancer actions.
พระราชบัญญัติยาเสพติดให้โทษ (ฉบับที ๗) พ.ศ. ๒๕๖๒. ราชกิจจานุเบกษาเล่ม 134 ตอนที่ 19 ก วันที18 กุมภาพันธ์ 2562[อินเทอร์เน็ต].[เข้าถึงเมื่อ1 พ.ค.2563]. เข้าถึงได้จาก:http://wwwwww.ratchakitcha.soc.go.th /DATA/PDF/2562/A/019/T_0001.PDF
Abdel-Hameed ESS, Bazaid SA, Shohayeb MM, El-Sayed MM,El-Wakil EA. Phytochemical Studies and Evaluation of Antioxidant,Anticancer and Antimicrobial Properties of Conocarpus erectus L. Growing in Taif, Saudi Arabia.Eur J Med Plants 2012; 93-112.
Baram L, Peled E, Berman P, Yellin B, Besser E, Benami M, et al. The heterogeneity and complexity of Cannabis extracts as antitumor agents. Oncotarget 2019; 10:4091–106.
Caffarel MM, Sarrió D, Palacios J, Guzmán M, Sánchez C. Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res 2006; 66:6615–21.
Caffarel MM, Moreno-Bueno G, Cerutti C, Palacios J, Guzman M, Mechta-Grigoriou F, et al. JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene 2008; 27:5033–44.
Carracedo A, Gironella M, Lorente M, Garcia S, Guzmán M, Velasco G, et al. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res 2006;66:6748–55.
De Petrocellis L, Ligresti A, Schiano Moriello A, Iappelli M, Verde R,Stott CG, et al. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br J Pharmacol2013; 168:79–102.
Elbaz M, Nasser MW, Ravi J, Wani NA, Ahirwar DK, Zhao H, et al.Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer. Mol Oncol 2015; 9:906–19.
Fonseca BM, Correia-da-Silva G, Teixeira NA. Cannabinoid-induced cell death in endometrial cancer cells:involvement of TRPV1 receptors in apoptosis. J Physiol Biochem 2018; 74:261–72.
Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int Cancer 2007; 121:2172–80.
Hart S, Fischer OM, Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 2004; 64:1943–50.
Leelawat S, Leelawat K, Narong S, Matangkasombut O. The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration. Cancer Invest 2010; 28:357–63.
Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, et al.Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 2006; 318:1375–87.
Lukhele ST, Motadi LR. Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells. BMC Complement Altern Med 2016;16:335.
Marcu JP. Christian RT, Lau D, Zielinski AJ, Horowitz MP, Lee J, et al. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther 2010; 9:180–9.
Noor R, Astuti I, Mustofa. Cytotoxicity of α-terpineol in Hela cell line and its effects to apoptosis and cell cycle.J Med Sci 2014;46:1–9.
Ramer R., Heinemann K., Merkord J., Rohde H., Salamon A.,Linnebacher M., Hinz B. COX-2 and PPAR-γ confer cannabidiolinduced apoptosis of human lung cancer cells. Mol Cancer Ther2013;12:69–82.
Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A.Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther 2011; 10:1161–72.
Takeda S, Yoshida K, Nishimura H, Harada M, Okajima S, Miyoshi H,et al. Δ9-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ). Chem Res Toxicol 2013;26:1073–9.
Tanamatayarat T. Cytotoxic activity screening of some rubiaceae plants in Northern Thailand. Thesis of Master of Phamacy in Phamaceutical Chemistry, Chiang Mai University, Chiang Mai; 2002.
Widiyastuti Y, Sholikhah IYM, Haryanti S. Cytotoxic activities of ethanolic and dichloromethane extract of leaves, stems, and flowers of Jarong [Stachytarpheta jamaicensis (L.) Vahl.] on HeLa and T47D cancer cell line.ICSAS 2019; 2202: 020101.
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
ข้อความและข้อคิดเห็นต่างๆ เป็นของผู้เขียนบทความ ไม่ใช่ความเห็นของกองบรรณาธิการหรือของวารสารกรมการแพทย์