Cannabis L. (Cannabis sativa)
The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. CSV JSON

Cannabis is the most widely used illicit drug in the world. Cannabinoids are used therapeutically by some patients as they have analgesic, anti-emetic and appetite stimulant properties which palliate adverse symptoms. Use of these agents in an oncology setting raises the question of whether they act to modulate the effectiveness of concurrently administered anti-cancer drugs. The transporter, P-glycoprotein (P-gp) confers multiple drug resistance (MDR) by effluxing a diverse array of anti-cancer agents. This study was undertaken to examine the effect of cannabinoids on P-gp. Unlike the known P-gp inhibitor, PSC833, short 1h exposure to three plant-derived cannabinoids, cannabinol (CBN), cannabidiol (CBD) and Delta(9)-tetrahydrocannabinol (THC) and the synthetic cannabinoid receptor agonist, WIN55, 212-2 (WIN) did not inhibit the efflux of the P-gp substrate Rhodamine 123 (Rh123) in either a drug-selected human T lymphoblastoid leukaemia cell line (CEM/VLB(100)) or in a mouse fibroblast MDR1 transfected cell line (77.1). However, in CEM/VLB(100) cells, prolonged 72 h exposure to the cannabinoids, THC and CBD, decreased P-gp expression to a similar extent as the flavonoid, curcumin (turmeric). This correlated with an increase in intracellular accumulation of Rh123 and enhanced sensitivity of the cells to the cytotoxic actions of the P-gp substrate, vinblastine. Taken together, these results provide preliminary evidence that cannabinoids do not exacerbate P-gp mediated MDR. Further, plant-derived cannabinoids are moderately effective in reversing MDR in CEM/VLB(100) cells by decreasing P-gp expression.

1 . CEM/VLB100: CBD (id=NPDI-UIHjqQ)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

cannabidiol

  • P-gp (ABCB1)

Cell system Other cells

CEM/VLB100 cell line (multidrug resistant sub line)

Results

Table 1.
%inhibition estimated from Fig 1b at 10 μM

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories

2 . CCRF-CEM: CBD (id=NPDI-gOdMHw)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

cannabidiol

  • P-gp (ABCB1)

Cell system Other cells

Acute T lymphoblastoid leukaemia cell line

Results

Table 1.

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories

3 . CEM/VLB100: CBN (id=NPDI-G8_czw)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

cannabinol

  • P-gp (ABCB1)

Cell system Other cells

CEM/VLB100 cell line (multidrug resistant sub line)

Results

Table 1.
Accumulation estimated from Fig 1a at 10 μM

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories

4 . CCRF-CEM: CBN (id=NPDI-EqzxjQ)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

cannabinol

  • P-gp (ABCB1)

Cell system Other cells

Acute T lymphoblastoid leukaemia cell line (CCRF-CEM)

Results

Table 1

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37 deg C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories

5 . CEM/VLB100: THC (id=NPDI-NC4pjQ)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

  • P-gp (ABCB1)

Cell system Other cells

CEM/VLB100 cell line (multidrug resistant sub line)

Results

Table 1.
Accumulation estimated from Fig 1c at 10 μM

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories

6 . CCRF-CEM: THC (id=NPDI-8Ej-Bg)

In Vitro Transporter Inhibition Experiment

Non-inhibition was detected.  Cutoff used — Not specified

Rhodamine 123

  • P-gp (ABCB1)

Cell system Other cells

Acute T lymphoblastoid leukaemia cell line

Results

Table 1.

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

5 x 10^4 cells/well

96-well

3 days

Assay Conditions

60 min

37C

1 μM

0.1-10 μM

Australian Government Analytical Laboratories