In vitro Activity of Novel Cannabinoids Derived from Tetrahydrocannabinolic Acid on Various Human Tumor Cell Lines

Source:
By:Author(s)

DOI: https://doi.org/10.30564/jor.v3i2.3629

Abstract: The in vitro study of tetracannabinolic acid (THCA) derivatives ALAM027 and ALAM108 was carried out on the following human tumor cells: T47D (breast, ductal carcinoma), PC-3 (prostate, adenocarcinoma), HT29 (colorectal carcinoma), Caco-2 (colon, adenocarcinoma), A549 (lung, carcinoma), U87MG (human glioblastoma) and U266B1 (multiple myeloma). The in vitro effects of THCA derivatives ALAM027 and ALAM108 on cell growth inhibition and IC50 values were measured using the CellTiter Glo assay. The ALAM027 compound showed good growth inhibition in all cell lines tested with the exception of U87MG cells. The ALAM108 compound also suppressed the growth of U87 MG cells but had little effect on T47D tumor cells. In vitro studies of THCA derivatives ALAM027 and ALAM108 showed antitumor activity in all cell lines tested. The difference in the activity of these compounds in relation to the T47D and U87MG tumor cells may be indicative of different functional mechanisms. References:

[1]Alexander Aizikovich. Process of purification of cannabinolic acids from plant material extract. WO2020016875. [2]Alexander Aizikovich. Cannabinolic acid derivatives and used thereof. WO 2019234728. [3]Alexander Aizikovich. Anticancer Effect of New Cannabinoids Derived from Tetrahydrocannabinolic Acid on PANC-1 and AsPC-1 Human Pancreas Tumor Cells. Journal of Pancreatic Cancer. 2020, 6, pp. 40-44. DOI: 10.1089/pancan.2020.00034. [4] Emily S. Seltzer, Andrea K. Watters, Danny MacKenzie Jr., Lauren M. Granat, Dong Zhang. Cannabidiol (CBD) as a Promising Anti-Cancer Drug. Cancers. 2020, 12, 3203, pp.1-26; DOI: 10.3390/cancers12113203. [5] Paweł Sledzinnski, Joanna Zeyland, Ryszard Słomski and Agnieszka Nowak. The current state and future perspectives of cannabinoids in cancer biology. Cancer medicine. 2017, 7, pp. 765-775. DOI: 10.1002/cam4.1312. [6]Olga Kovalchuk, Igor Kovalchuk. Cannabinoids as anticancer therapeutic agents. Cell Cycle. 2020, pp. 1-29. doi.org/10.1080/15384101.2020.1742952. [7]Claudia A. Dumitru, I. Erol Sandalcioglu and Meliha Karsak. Cannabinoids in Glioblastoma Therapy: New Applications for Old Drugs. Frontiers in Molecular Neuroscience. 2018, 11, 159, pp. 1-7. DOI: 10.3389/fnmol.2018.00159. [8]Sungryul Yu, Taemook Kim, Kyung Hyun Yoo, Keunsoo Kang. The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochemical and Biophysical Research Communications. 2017, 486, pp. 752-758. http://dx.doi.org/10.1016/j.bbrc.2017.03.114. [9]Terezia Kiskova, , Felicitas Mungenast, Maria Suvakova, Walter Jäger and Theresia Thalhammer. Future Aspects for Cannabinoids in Breast Cancer Therapy.Int. J. Mol. Sci. 2019, 20, 1673, pp.1-21; DOI: 10.3390/ijms20071673. [10]Maria M. Caffarel, David Sarrio, Jose Palacios, Manuel Guzman, and Cristina Sanchez. Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation. Cancer Res. 2006, 66, pp.6615-6621. DOI: 10.1158/0008-5472.CAN-05-4566. [11]Ahmed S. Sulta, Mona A. Marie, Salah A. Sheweita. Novel mechanism of cannabidiol-induced apoptosis in breast cancer cell lines. The Breast. 2018, 41, pp. 34-41. doi.org/10.1016/j.breast.2018.06.009. [12]Maria G. Sanchez, Lidia Ruiz-Llorente, Ana M. Sanchez, Ines Diaz-Laviada. Activation of phosphoinositide 3-kinase/PKB pathway by CB1 and CB2 cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf-1 stimulation and NGF induction. Cellular Signalling. 2003, 15, pp. 851–859. DOI: 10.1016/S0898-6568(03)00036-6. [13]Lidia Ruiz, Alberto Miguel, Ines Diaz-Laviada. 9-Tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Letters. 1999, 458, pp. 400-404. PII: S0 014-5793(99)01073–X. [14]Daniela Cerretani, Giulia Collodel, Antonella Brizzi, Anna Ida Fiaschi, Andrea Menchiari, Elena Moretti, Laura Moltoni and Lucia Micheli. Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83. Int. J. Mol. Sci. 2020, 21, 5533, pp.1-15; DOI: 10.3390/ijms21155533. [15]Wesley M. Raup-Konsavage, Megan Johnson, Christopher A. Legare. Gregory S. Yochum, Daniel J. Morgan, and Kent E. Vrana. Synthetic Cannabinoid Activity Against Colorectal Cancer Cells. Cannabis and Cannabinoid Research. 2018, 3.1, pp.272-281. DOI: 10.1089/can.2018.0065. [16]Sofia B. Gustafsson, Theres Lindgren, Maria Jonsson, Stig O. P. Jacobsson. Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human colorectal carcinoma cells: synergism with 5-Fluorouracil. Cancer Chemother Pharmacol. 2009, 63. pp.691–701. DOI: 10.1007/s00280-008-0788-5. [17]Gabriella Aviello, Barbara Romano, Francesca Borrelli, Raffaele Capasso, Laura Gallo, Fabiana Piscitelli, Vincenzo Di Marzo, Angelo A. Izzo. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. J Mol Med. 2012, 90, pp. 925–934 DOI: 10.1007/s00109-011-0856-x. [18]Liran Baram, Ella Peled, Paula Berman, Ben Yellin, Elazar Besser, Maya Benami, Igal Louria-Hayon, Gil M. Lewitus1 and David Meiri. The heterogeneity and complexity of Cannabis extracts as antitumor agents. Oncotarget, 2019, 10. pp: 4091-4106. DOI: 10.18632/oncotarget.26983. [19]Anju Preet, Zahida Qamri, Mohd W Nasser, Anil Prasad, Konstantin Shilo, Xianghong Zou, Jerome E. Groopman, and Ramesh K. Ganju. Cannabinoid Receptors, CB1 and CB2, as Novel Targets for Inhibition of Non–Small Cell Lung Cancer Growth and Metastasis. Cancer Prevention Research. 2010, 4, pp. 65-75. DOI: 10.1158/1940-6207.CAPR-10-0181. [20]Lara Milian, Manuel Mata, Javier Alcacer, Maria Oliver, Maria Sancho-Tello, Jos Javier Martin de Llano, Carlos Camps, Jose Galbis, Julian Carretero, Carmen Carda. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. Plos One. 2020,12, pp. 1-17. doi.org/10.1371/journal. pone.0228909. [21]CJ Fowler. ∆ 9 -Tetrahydrocannabinol and cannabidiol as potential curative agents for cancer. A critical examination of the preclinical literature. “Accepted Article”. DOI: 10.1002/cpt.84. [22]Katherine A. Scott, Angus G. Dalgleish, and Wai M. Liu The Combination of Cannabidiol and 9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model. Molecular Cancer Therapeutics. 2014, 12, pp. 2955-2967. DOI: 10.1158/1535-7163.MCT-14-0402. [23]Elena Monti, Tiziana Rubino, Daniela Parolaro. Cannabidiol, a Non-Psychoactive Cannabinoid Compound, Inhibits Proliferation and Invasion in U87- MG and T98G Glioma Cells through a Multitarget Effect. PLOS ONE. 2013, 8, pp 1-9. DOI: 10.1371/journal.pone.007691. [24] Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni. Cannabinoids synergize with car lzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016, 7, pp. 77543-77557. DOI: 10.18632/oncotarget.12721. [25] Ji-Hu Zhang, Thomas D. Y. Chung and Kevin R. Oldenburg. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen,1999, 4, pp. 67-73. DOI: 10.1177/108705719900400206.