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Distribution of Curcumin and THC in Peripheral Blood Mononuclear Cells Isolated from Healthy Individuals and Patients with Chronic Lymphocytic Leukemia.

Abstract Background/Aim: Curcumin is being widely investigated for its anticancer properties and studies in the literature suggest that curcumin distributes to a higher degree in tumor versus non-tumor cells. In the current study, we report on investigation of the distribution of curcumin and metabolism to THC in PBMC from healthy individuals and chronic lymphocytic leukemia (CLL) patients following exposure to Lipocurc™ (liposomal curcumin). Materials and Methods: The time and temperature-dependent distribution of liposomal curcumin and metabolism to tetrahydrocurcumin (THC) were measured in vitro in human peripheral blood mononuclear cells (PBMC) obtained from healthy individuals, PBMCHI(cryopreserved and freshly isolated PBMC) and CLL patients (cryopreserved PBMC) with lymphocyte counts ranging from 17-58×106 cells/ml (PBMCCLL,Grp 1) and >150×106 cells/ml (PBMCCLL,Grp 2). PBMC were incubated in plasma protein supplemented media with Lipocurc™ for 2-16 min at 37°C and 4°C and the cell and medium levels of curcumin determined by LC-MS/MS. Results: PBMC from CLL patients displayed a 2.2-2.6-fold higher distribution of curcumin compared to PBMCHICurcumin distribution into PBMCCLL, Grp 1/Grp 2 ranged from 384.75 - 574.50 ng/g w.w. of cell pellet and was greater compared to PBMCHIthat ranged from 122.27-220.59 ng/g w.w. of cell pellet following incubation for up to 15-16 min at 37°C. The distribution of curcumin into PBMCCLL,Grp 2 was time-dependent in comparison to PBMCHIwhich did not display a time-dependence and there was no temperature-dependence for curcumin distribution in either cell type. Curcumin was metabolized to THC in PBMC. The metabolism of curcumin to THC was not markedly different between PBMCHI(range=23.94-42.04 ng/g w.w. cell pellet) and PBMCCLL,Grp 1/Grp 2 (range=23.08-48.22 ng/g. w.w. cell pellet). However, a significantly greater time and temperature-dependence was noted for THC in PBMCCLL,Grp 2 compared to PBMCHIConclusion: Curcumin distribution into PBMC from CLL patients was higher compared to PBMC from healthy individuals, while metabolism to THC was similar. The potential for a greater distribution of curcumin into PBMC from CLL patients may be of therapeutic benefit.
PMID
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Authors

Mayor MeshTerms
Keywords

Curcumin

blood cells

chronic lymphocytic leukemia

tetrahydrocurcumin

Journal Title anticancer research
Publication Year Start




PMID- 29277764
OWN - NLM
STAT- MEDLINE
DCOM- 20180101
LR  - 20180104
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 38
IP  - 1
DP  - 2018 Jan
TI  - Distribution of Curcumin and THC in Peripheral Blood Mononuclear Cells Isolated
      from Healthy Individuals and Patients with Chronic Lymphocytic Leukemia.
PG  - 121-130
AB  - Background/Aim: Curcumin is being widely investigated for its anticancer
      properties and studies in the literature suggest that curcumin distributes to a
      higher degree in tumor versus non-tumor cells. In the current study, we report on
      investigation of the distribution of curcumin and metabolism to THC in PBMC from 
      healthy individuals and chronic lymphocytic leukemia (CLL) patients following
      exposure to Lipocurc (liposomal curcumin). Materials and Methods: The time and
      temperature-dependent distribution of liposomal curcumin and metabolism to
      tetrahydrocurcumin (THC) were measured in vitro in human peripheral blood
      mononuclear cells (PBMC) obtained from healthy individuals, PBMCHI(cryopreserved 
      and freshly isolated PBMC) and CLL patients (cryopreserved PBMC) with lymphocyte 
      counts ranging from 17-58x10(6) cells/ml (PBMCCLL,Grp 1) and >150x10(6) cells/ml 
      (PBMCCLL,Grp 2). PBMC were incubated in plasma protein supplemented media with
      Lipocurc for 2-16 min at 37 degrees C and 4 degrees C and the cell and medium
      levels of curcumin determined by LC-MS/MS. Results: PBMC from CLL patients
      displayed a 2.2-2.6-fold higher distribution of curcumin compared to
      PBMCHICurcumin distribution into PBMCCLL, Grp 1/Grp 2 ranged from 384.75 - 574.50
      ng/g w.w. of cell pellet and was greater compared to PBMCHIthat ranged from
      122.27-220.59 ng/g w.w. of cell pellet following incubation for up to 15-16 min
      at 37 degrees C. The distribution of curcumin into PBMCCLL,Grp 2 was
      time-dependent in comparison to PBMCHIwhich did not display a time-dependence and
      there was no temperature-dependence for curcumin distribution in either cell
      type. Curcumin was metabolized to THC in PBMC. The metabolism of curcumin to THC 
      was not markedly different between PBMCHI(range=23.94-42.04 ng/g w.w. cell
      pellet) and PBMCCLL,Grp 1/Grp 2 (range=23.08-48.22 ng/g. w.w. cell pellet).
      However, a significantly greater time and temperature-dependence was noted for
      THC in PBMCCLL,Grp 2 compared to PBMCHIConclusion: Curcumin distribution into
      PBMC from CLL patients was higher compared to PBMC from healthy individuals,
      while metabolism to THC was similar. The potential for a greater distribution of 
      curcumin into PBMC from CLL patients may be of therapeutic benefit.
CI  - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Bolger, Gordon T
AU  - Bolger GT
AD  - Nucro-Technics, Scarborough, ON, Canada [email protected]
      [email protected]
FAU - Licollari, Albert
AU  - Licollari A
AD  - Nucro-Technics, Scarborough, ON, Canada.
FAU - Tan, Aimin
AU  - Tan A
AD  - Nucro-Technics, Scarborough, ON, Canada.
FAU - Greil, Richard
AU  - Greil R
AD  - IIIrd Medical Department with Hematology and Medical Oncology, Oncologic Center, 
      Paracelsus Medical University, Salzburg, Salzburg Cancer Research Institute,
      Cancer Cluster Salzburg, Salzburg, Austria.
FAU - Pleyer, Lisa
AU  - Pleyer L
AD  - IIIrd Medical Department with Hematology and Medical Oncology, Oncologic Center, 
      Paracelsus Medical University, Salzburg, Salzburg Cancer Research Institute,
      Cancer Cluster Salzburg, Salzburg, Austria.
FAU - Vcelar, Brigitta
AU  - Vcelar B
AD  - Polymun Scientific Immunbiologische Forschung GmbH, Klosterneuburg, Austria.
FAU - Majeed, Muhammad
AU  - Majeed M
AD  - Sabinsa Corporation, East Windsor, NJ, U.S.A.
FAU - Sordillo, Peter
AU  - Sordillo P
AD  - SignPath Pharma Inc., New York, NY, U.S.A. [email protected]
      [email protected]
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Liposomes)
RN  - 00U0645U03 (tetrahydrocurcumin)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Curcumin/*administration & dosage/*analogs & derivatives/metabolism/pharmacology
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*metabolism
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Liposomes
OTO - NOTNLM
OT  - *Curcumin
OT  - *blood cells
OT  - *chronic lymphocytic leukemia
OT  - *tetrahydrocurcumin
EDAT- 2017/12/27 06:00
MHDA- 2018/01/02 06:00
CRDT- 2017/12/27 06:00
PHST- 2017/10/20 00:00 [received]
PHST- 2017/11/02 00:00 [revised]
PHST- 2017/11/06 00:00 [accepted]
PHST- 2017/12/27 06:00 [entrez]
PHST- 2017/12/27 06:00 [pubmed]
PHST- 2018/01/02 06:00 [medline]
AID - 38/1/121 [pii]
AID - 10.21873/anticanres.12199 [doi]
PST - ppublish
SO  - Anticancer Res. 2018 Jan;38(1):121-130. doi: 10.21873/anticanres.12199.