resveratrol and curcumin synergy

The following paper looks at how liposomal formulations of curcumin and synergise against cancer cells:

Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice.
Narayanan NK, Nargi D, Randolph C, Narayanan BA.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Narayanan.Narayanan@nyumc.org

Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clinical use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examined the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC analysis of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Molecular targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.

Now there is obviously an effect due to the liposome encapsulation of each substance, but the interesting thing is that serum levels of the substances combined were higher than the individual liposomal agents. This begs the question does the same thing happen in non-liposomal forms of curcumin and resveratrol? Though availability won't be as high as in the liposomal forms, does the combination of high-purity powders work better together than separately?

The following paper looks at how liposomal formulations of curcumin and synergise against cancer cells:

Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice.
Narayanan NK, Nargi D, Randolph C, Narayanan BA.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Narayanan.Narayanan@nyumc.org

Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clinical use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examined the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC analysis of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Molecular targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.

Now there is obviously an effect due to the liposome encapsulation of each substance, but the interesting thing is that serum levels of the substances combined were higher than the individual liposomal agents. This begs the question does the same thing happen in non-liposomal forms of curcumin and resveratrol? Though availability won't be as high as in the liposomal forms, does the combination of high-purity powders work better together than separately

It is not possible to tell from the abstract alone if the combination worked better than either alone, though it seemed to be implied by the abstract; they do not seem to have measured individual phytochemicals in the knockout mice, only the combination. I would expect the liposomes do not affect the biochemical pathways, only the serum levels. This may be important, but liposomal delivery is only one of several strategies to improve bio-availability.

thx for this post, interesting.

Another paper just published that points the same way:

Curcumin synergizes with resveratrol to inhibit colon cancer.
Majumdar AP, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, Yu Y, Elliott AA, Levi E, Sarkar FH.

John D. Dingell VA Medical Center, Detroit, Michigan, USA.

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

PMID: 19838927 [PubMed - in process]

If anyone can get hold of the full paper I'd love a chance to read the full thing rather than just the abstract...

Edited by ppp, 20 October 2009 - 01:17 PM.

Thanks for the studies! I recently released a product called Alzenia with both Resveratrol and Curcumin. Good to see some synergy studies.

Edited by synapse, 20 October 2009 - 01:16 PM.