Cannabidiol Interacts Antagonistically with Cisplatin and Additively with Mitoxantrone in Various Melanoma Cell Lines—An Isobolographic Analysis

Abstract

The medical application of cannabidiol (CBD) has been gathering increasing attention in recent years. This non-psychotropic cannabis-derived compound possesses antiepileptic, antipsychotic, anti-inflammatory and anxiolytic properties. Recent studies report that it also exerts antineoplastic effects in multiple types of cancers, including melanoma. In this in vitro study we tried to reveal the anticancer properties of CBD in malignant melanoma cell lines (SK-MEL 28, A375, FM55P and FM55M2) administered alone, as well as in combination with mitoxantrone (MTX) or cisplatin (CDDP). The effects of CBD on the viability of melanoma cells were measured by the MTT assay; cytotoxicity was determined in the LDH test and proliferation in the BrdU test. Moreover, the safety of CBD was tested in human keratinocytes (HaCaT) in LDH and MTT tests. Results indicate that CBD reduces the viability and proliferation of melanoma-malignant cells and exerts additive interactions with MTX. Unfortunately, CBD produced antagonistic interaction when combined with CDDP. CBD does not cause significant cytotoxicity in HaCaT cell line. In conclusion, CBD may be considered as a part of melanoma multi-drug therapy when combined with MTX. A special attention should be paid to the combination of CBD with CDDP due to the antagonistic interaction observed in the studied malignant melanoma cell lines.

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

“…Combination therapy involving drugs acting by a different mechanism is currently one of the most promising therapeutic strategies in oncology, which may prevent the occurrence of severe side effects associated with monotherapy and reduce the likelihood of developing cancer cell resistance [ 36 ]. Currently, in the treatment of melanoma, combinations of chemotherapeutic agents with coumarins (e.g., osthole) [ 30 ], cannabinoids such as CBD [ 37 ] or with amantadine (a drug used in Parkinson’s disease) [ 38 ] are being tested.…”

“…The 72 h incubation time is the average doubling time for all melanoma cell lines tested. In the case of the A375 line, this time is the shortest 6–12 h [ 55 ], for the SK-Mel28 it is 17.5 h [ 56 ], but in the case of the FM55M2 and FM55P lines, most of the experiments encountered are the incubation time of 72 h [ 37 , 38 , 57 ]. After 72 h incubation, cells were incubated for 3 h with MTT solution (5 mg/mL, Sigma-Aldrich, USA).…”

Cannabidiol and Minor Phytocannabinoids: A Preliminary Study to Assess Their Anti-Melanoma, Anti-Melanogenic, and Anti-Tyrosinase Properties

“…In a previous study, CBD reduced the viability and proliferation of malignant melanoma (A375, FM55P, SK-MEL-28, and FM55M2) cells in a concentration-dependent manner; the IC 50 values in these cell lines were between 3.81 and 7.75 µg/mL. In addition, the viability of human immortalized HaCaT keratinocytes was not significantly affected [ 34 ]. The lack of CBD toxicity towards non-cancer skin cells also agrees with the research of Vacek et al [ 35 ], when no reduction in the viability of HaCaT keratinocytes and normal human dermal fibroblasts was observed over the concentration range of 0.78–100 μM.…”

Fraxetin Interacts Additively with Cisplatin and Mitoxantrone, Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis

“…* 200 µM was the maximum possible concentration in the medium considering the 0.1% DMSO and the solubility limit of scoparone. The experimentally derived mean inhibitory concentration (IC 50 ) ranging from 1.3 to 3.3 µM for CDDP, from 0.03 to 1.7 µM for MTX, and from 1.27 to 15.87 nM for DOCX were mentioned in previous experiments [37,38].…”