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Monday 7 October 2019

Curcumin Starves Cancer Cells to Death - Life Extension

Researchers are intrigued by a promising discovery that curcumin selectively starves tumor cells to death.1

LIFE EXTENSION MAGAZINE
Winter 2018-2019 Special Edition
By Kirk Stokel
Over 4,500 published studies describe the anti-cancer effects of curcumin.
Researchers are intrigued by a promising discovery that curcumin selectively starves tumor cells to death.1
Curcumin does this by depriving cancer cells of the ability to make and use ATP, the energy currency within cells.2
Since most cancer cells generate ATP in a different way than healthy cells, curcumin selectively kills tumor cells with no impact on healthy tissues.
These newly uncovered energy-disrupting properties of curcumin further support the preventive potential of this botanical compound.

Cutting Cancer’s Energy Supply

Cancer cells require tremendous energy to promote their rapid, uncontrolled growth, and they have developed numerous methods to support that energy demand.
In particular, cancer cells have an unusual, oxygen-free mechanism of extracting energy from glucose to produce ATP (adenosine triphosphate). This process helps most cancer cells survive in the low-oxygen environments they generate as they grow rapidly.2
Scientists conducted a study to determine if this process can be reversed in cancer cells.
Since many different types of cancer use the same metabolic trick to extract energy, the researchers studied curcumin’s impact on a variety of tumor lines, including leukemia, breast, melanoma (skin), and colon cancers.2
This study shed new light on curcumin’s ability to starve cancer into submission by interfering with how tumors cells use energy.
Let’s look at the findings one at a time.

Curcumin Blocks ATP Production

Foods considered as a part of the Mediteranian diet
First, the researchers found that curcumin can sharply reduce how much energy is available to the cancer cells.2
This study showed that curcumin was able to:
1) Reduce levels of ATP-synthase (the enzyme that creates ATP) in all four tumor cell lines in culture,
2) Reduce cellular levels of ATP in three of the four cell lines, and
3) Lower the ratio of high-energy ATP to lower-energy AMP in all four cell lines.

Curcumin Slows Tumor Growth

Next, researchers implanted aggressive skin cancer (melanoma) cells into live mice. Half the mice were treated with curcumin and the other half served as the control group.2
Just 2 days into the study, the curcumin-treated mice were demonstrating significantly slower tumor growth. Tumor growth remained significantly slower for the entire period of the study.
Not surprisingly, ATP-synthase, ATP levels, and the ATP/AMP ratio were all significantly lowered in the curcumin group. These results indicate that energy starvation was a mechanism of action by which curcumin slowed tumor growth.

Curcumin Prevents New Blood Vessel Growth

Cancers need to trigger new blood vessel development (called angiogenesis) to support their nutrient needs as they rapidly grow. Blocking this process is an important way to limit the growth and spread of a tumor.
After removing tumors from the mice in this study, the researchers found that the curcumin-supplemented animals’ tumors had fewer new blood vessels compared with control-fed mice.
This indicates that curcumin reduced the tumors nutrient energy access by limiting blood flow.2

Curcumin’s Known Tumor-Fighting Properties

This most recent study adds to an abundance of evidence pointing to curcumin’s potent cancer-fighting abilities. It focuses on curcumin’s unique ability to combat a variety of cancers by cutting off their energy supply.
Previous studies have shown curcumin’s tumor-fighting properties in multiple specific types of cancer. Here are some highlights from the most recent literature.

Colorectal Cancer

Cancers of the colon and rectum are among the most common malignancies in men and women. Curcumin has a long track record of achievements in preventing colorectal cancers.
A Phase IIa human clinical trial has shown that 4 grams/day of curcumin significantly reduces the number of aberrant crypt foci found during endoscopy. This is a critical finding because if aberrant crypt foci are left untreated, they can produce malignant tumors.3
Weight loss is common in cancer patients. A human study showed that colon cancer patients who were supplemented with curcumin gained more weight, had less inflammation, and had increased numbers of cancer cells dying by apoptosis.4 This effect has been traced to curcumin’s ability to activate a “programmed cell death” gene in tumor cells.
Finally, curcumin has been shown to selectively reduce the survival of cancer stem cells.5 These cells account for much of the metastatic spread and tumor recurrences seen in aggressive malignancies. Cutting their numbers is an appealing approach to preventing tumors from spreading.
While a high-dose (4,000 mg) of curcumin was used in this study, more bioavailable curcumin forms can enable one to achieve a similar dose with two capsules a day.
WHAT YOU NEED TO KNOW
SIDEBAR IMAGE ALT TEXT

Curcumin Starves Cancer Cells to Death

  • Curcumin is a powerful, multi-functional polyphenol that is gaining increasing recognition for its cancer chemopreventive properties.
  • A new study shows that curcumin sharply restricts cancer cells’ ability to extract energy from glucose in the blood.
  • This mechanism is especially appealing for cancer chemoprevention because it would target the great majority of cancers.
  • Previous studies also show that curcumin can reduce inflammation, prevent chemical stress, shut down cancer-promoting pathways, and interfere with malignant cells’ growth and development.
  • These multiple mechanisms of action make it clear that curcumin should be a central element of any comprehensive cancer chemoprevention regimen.

Breast Cancer

Breast cancer is the most common cancer in women, and it’s the second leading cause of cancer deaths among women worldwide.6,7
Curcumin has shown promise in combatting breast cancer. This is especially true of estrogen receptor-negative tumors, which respond poorly to cancer chemotherapy.6
Studies show that giving curcumin to animals with implanted human breast cancers shrinks the tumors, deprives them of their blood supply, and triggers their self-destruction by apoptosis.6,8
More recently, research revealed that curcumin can also combat breast cancer by reversing the excessive methylation of certain genes that is associated with increased cancer development.9

Prostate Cancer

Prostate cancer strikes one in nine American men, yet is among the most preventable cancers because of its slow growth.10
Curcumin has multiple actions against prostate cancer. It defends prostate cells against the dysfunctional proteins produced during cancer progression. It also slows invasion of nearby healthy tissue by the cancer, which helps to keep the tumor at a lower grade (meaning it grows more slowly and has a better prognosis).11-13
One study showed that when human prostate cells were implanted into mice, they grew into sizable tumors. But when these animals were supplemented with curcumin, the tumors grew 27% more slowly. In addition, the time it took to double levels of prostate specific antigen (PSA) was extended or delayed by about two-fold.14 (Doubling time is an indicator of how aggressive the cancer is.)
Curcumin can also reduce tumor-derived testosterone production in prostate cancer cells.15 This is a hidden source of male hormones that often contributes to treatment-resistant disease.16 This development offers a welcome new approach to treating these challenging tumors.

Liver Cancer

Liver cancer is increasing in incidence worldwide, spurred by epidemic hepatitis C virus and rampant fatty liver disease.17 
In lab studies, curcumin was shown to help prevent liver cancer by reducing inflammatory signaling, inhibiting cell growth, and activating cell death by apoptosis.18-20 It has also been shown to reduce populations of liver cancer stem cells.19,21
In one study, curcumin inhibited the growth of liver cancer cells, while also promoting their death by apoptosis. And in a mouse model of liver cancer, treatment with curcumin caused the tumors to grow much more slowly.22
And, in an exciting development, a study published in 2018 showed that when curcumin is combined with the AMPK-activator drug metformin, the combination worked better than either alone in preventing growth, metastasis, and new blood vessel formation in hepatocellular carcinoma, the most common—and most deadly—type of liver cancer.23

Lung Cancer

December 2013 Life Extension Life Extension’s rebuttal to FDA and Patrick Walsh, M.D.
A new study shows that
curcumin sharply restricts
cancer cells’ ability to
extract energy from
glucose in the blood.
Lung cancer continues to be the top cause of cancer-related deaths, making it a huge priority for prevention.24,25
An abundance of animal and basic lab studies show curcumin’s potential against lung cancer.
For example, curcumin has been shown to reduce the growth of implanted human lung cancers in mice.26  Lab studies on lung cancer show that curcumin alters proteins required for metastasis, boosting the function of immune cells that are inactivated by cancers, and targeting blood vessel growth.24,26,27
A unique way in which curcumin combats lung cancer is by modulating microRNA inside cancer cells.28-30 These short stretches of genetic material regulate how the main genes in tumor cells are translated into functional proteins.
Studies reveal that curcumin inhibits lung cancer cell growth by downregulating a gene that promotes tumor formation, while upregulating genes that suppress transformation.28 Other research shows similar favorable modulation of miRNAs involved in metastatic spread.30

Summary

Curcumin is the polyphenol that gives the yellow color to the spice turmeric. It has been front and center in the scientific press for years—mostly recognized for its ability to suppress inflammation.2,31,32
Curcumin has also been shown to prevent cancer progression through a variety of mechanisms. Most recently, a study found that curcumin starves cancer cells of much-needed energy.
This mechanism is especially appealing for cancer prevention because it would target the great majority of cancers.
This confirms previous studies showing that curcumin has specific effects against colorectal, breast, prostate, lung, and liver cancers.
Starving malignant cells of their energy supply is an ideal way of boosting our bodies’ natural cancer resistance, helping it quench cancer long before a tumor is detectable.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Available at: https://www.ncbi.nlm.nih.gov/pubmed/?term=curcumin+and+cancer. Accessed September 21, 2018.
  2. Bianchi G, Ravera S, Traverso C, et al. Curcumin induces a fatal energetic impairment in tumor cells in vitro and in vivo by inhibiting ATP-synthase activity. Carcinogenesis. 2018 Sep 21;39(9):1141-50.
  3. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011 Mar;4(3):354-64.
  4. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011 Mar;29(3):208-13.
  5. James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015 Aug 10;364(2):135-41.
  6. Bimonte S, Barbieri A, Palma G, et al. Dissecting the role of curcumin in tumour growth and angiogenesis in mouse model of human breast cancer. Biomed Res Int. 2015;2015:878134.
  7. Wang Y, Yu J, Cui R, et al. Curcumin in Treating Breast Cancer: A Review. J Lab Autom. 2016 Dec;21(6):723-31.
  8. Ferreira LC, Arbab AS, Jardim-Perassi BV, et al. Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer. Anticancer Agents Med Chem. 2015;15(10):1285-96.
  9. Kumar U, Sharma U, Rathi G. Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line. Tumour Biol. 2017 Feb;39(2):1010428317692258.
  10. Available at: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed September 24, 2018.
  11. Sundram V, Chauhan SC, Ebeling M, et al. Curcumin attenuates beta-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS One. 2012;7(4):e35368.
  12. Liu T, Chi H, Chen J, et al. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene. 2017 Oct 5;631:29-38.
  13. Yang J, Wang C, Zhang Z, et al. Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway. APMIS. 2017 Feb;125(2):134-40.
  14. Hong JH, Lee G, Choi HY. Effect of curcumin on the interaction between androgen receptor and Wnt/beta-catenin in LNCaP xenografts. Korean J Urol. 2015 Sep;56(9):656-65.
  15. Ide H, Lu Y, Noguchi T, et al. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer. Cancer Sci. 2018 Apr;109(4):1230-8.
  16. Armandari I, Hamid AR, Verhaegh G, et al. Intratumoral steroidogenesis in castration-resistant prostate cancer: a target for therapy. Prostate Int. 2014 Sep;2(3):105-13.
  17. Global Burden of Disease Liver Cancer C, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol. 2017 Dec 1;3(12):1683-91.
  18. Dai XZ, Yin HT, Sun LF, et al. Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac J Cancer Prev. 2013;14(6):3855-9.
  19. Marquardt JU, Gomez-Quiroz L, Arreguin Camacho LO, et al. Curcumin effectively inhibits oncogenic NF-kappaB signaling and restrains stemness features in liver cancer. J Hepatol. 2015 Sep;63(3):661-9.
  20. Elmansi AM, El-Karef AA, Shishtawy M, et al. Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways. Ann Hepatol. 2017 Jul-Aug;16(4):607-18.
  21. Tsai CF, Hsieh TH, Lee JN, et al. Curcumin Suppresses Phthalate-Induced Metastasis and the Proportion of Cancer Stem Cell (CSC)-like Cells via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma. J Agric Food Chem. 2015 Dec 9;63(48):10388-98.
  22. Pan Z, Zhuang J, Ji C, et al. Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression. Oncol Lett. 2018 Apr;15(4):4821-6.
  23. Zhang HH, Zhang Y, Cheng YN, et al. Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo. Mol Carcinog. 2018 Jan;57(1):44-56.
  24. Liu D, You M, Xu Y, et al. Inhibition of curcumin on myeloid-derived suppressor cells is requisite for controlling lung cancer. Int Immunopharmacol. 2016 Oct;39:265-72.
  25. Available at: https://www.cancer.org/latest-news/facts-and-figures-2018-rate-of-deaths-from-cancer-continues-decline.html. Accessed September 24, 2018.
  26. Chen QY, Jiao DM, Yao QH, et al. Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines. Int J Oncol. 2012 May;40(5):1561-8.
  27. Xu X, Zhu Y. Curcumin inhibits human non-small cell lung cancer xenografts by targeting STAT3 pathway. Am J Transl Res. 2017;9(8):3633-41.
  28. Lelli D, Pedone C, Majeed M, et al. Curcumin and Lung Cancer: the Role of microRNAs.Curr Pharm Des. 2017;23(23):3440-4.
  29. Liu WL, Chang JM, Chong IW, et al. Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549. Molecules. 2017 Jun 3;22(6).
  30. Zhan JW, Jiao DM, Wang Y, et al. Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti-lung cancer cell invasion. Thorac Cancer. 2017 Sep;8(5):461-70.
  31. Chadalapaka G, Jutooru I, Chintharlapalli S, et al. Curcumin decreases specificity protein expression in bladder cancer cells. Cancer Res. 2008 Jul 1;68(13):5345-54.
  32. Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-alpha, NF-kappaB, and oxidative stress. Can J Physiol Pharmacol. 2017 Feb;95(2):14

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