Written by Joyce Smith, BS. Treatment of malignant pleural mesothelioma cells with artichoke leaf extract significantly decreased cell growth and proliferation and increased apoptosis (cell death). 

There is presently no diagnostic tool that allows for early diagnosis of malignant pleural mesothelioma (MPM) (1, 2). This rare and treatment-resistant disease is on the increase, particularly in developing countries where asbestos is still exported and not yet banned (3, 4). Today there is increased interest in natural products as potential cancer agents because they offer lower toxicity, while simultaneously targeting many of the signaling pathways that affect the growth, programmed death, and spread of cancer cells (16, 17). Coffee, resveratrol, curcumin, and butein have all demonstrated anti-cancer activity against mesothelioma cell lines (5, 6, 7). Observational studies have shown that following a Mediterranean diet is associated with a significant reduction in the risk of overall cancer mortality (10%, colorectal cancer (14%), prostate cancer (4%) and digestive tract cancer (56%) (8).

In this study, researchers demonstrate in both in vitro and in vivo in animal models that globe artichoke, Cynara scolymus), an important component of the Mediterranean diet (9), exhibits anti-tumor activity by positively influencing the pathways involved in cell mutation and cancer and has therapeutic potential for the treatment of mesothelioma.

Researchers tested artichoke leaf extract against MPM cell lines in a number of ways to demonstrate its antitumoral activity.

Results:

Artichoke Leaf extract inhibited MPM cell growth and proliferation:

  • Both MPM cell lines and normal mesothelial cells, when treated with increasing concentrations of artichoke extract (3 – 200 ug/ml) for 72 hours, significantly showed decreased cell growth in a dose dependent manner. (P<0.05)
  • A colony-forming assay was performed to evaluate the ability of MPM cells to form colonies. The assay demonstrated that artichoke leaf extract significantly inhibits MPM cell lines from colonizing. (P<0.05)

Artichoke leaf extract induces apoptosis (programmed cell death) of MPM cells lines: (P<0.05)

  • Artichoke leaf extract caused cell death in a dose dependent manner in MPM cell lines by activating pathways (caspase3, caspase-7 and PARP) involved in apoptosis of MPM cells.

Artichoke leaf severely impairs migration and invasion of MPM cell lines: (P<0.05)

  • At concentrations of 6ug/ml and 12ug/ml, artichoke leaf extract significantly inhibited, in a time dependent manner, MPM cell migration by 50% and 35% respectively.

Artichoke leaf extract affects in vivo tumor growth of mesothelial cell lines: (P<0.05)

  • MPM cell lines were treated with artichoke leaf extract (50ug/ml) for 24 hours, then injected into mice. When tumor growth became visible, mice were subcutaneously transplanted with MPM cells and randomly divided into 5 groups of 6 mice per group. The control group received no artichoke extract while the other 4 groups were fed different concentrations (25, 50, and 75 mg/ml) of artichoke leaf extract. After 3 weeks the artichoke leaf extract significantly reduced in a dose dependent manner the growth of xenografted mesothelioma tumors in the mice.
  • Artichoke leaf extract, at a concentration of 75 mg/ml, also increased the ability of *pemetrexed to reduce the tumor size in mice.

Artichoke leaf extract produces changes in the metabolic profiles of MPM cells: (P< 0.013)

  • Since metabolic alterations are one of the hallmarks of the cancer cell, researchers assessed the ability of artichoke extract to affect the metabolism of MPM cells. They found a significant difference between artichoke-treated MPM cells and control.

Artichoke leaf extract antitumorial activity involves different signaling pathways:            

  • Researchers determined which signaling pathways are impacted by artichoke treatment. MPM cells were treated with 50 ug/ml of artichoke extract (or no artichoke) for 24 hours, then analyzed using a “phosphor-antibody array”. Researchers concluded that artichoke leaf extract’s strong antitumoral activities were linked to its ability to regulate multiple signaling pathways that are involved in cell death.

Because signaling pathways altered in mesothelioma are the same signaling pathways commonly altered in other human cancers, researchers believe artichoke leaf extract could have antitumoral effects on other types of cancer as well. They believe that artichoke leaf extract could be used in combination with anti-cancer agents such as *cisplatin or *pemetrexel to improve their effectiveness.

*Prescription drugs can save lives but may also cause unwanted side effects.  Thus, not all drugs are considered safe.  Consult with your medical healthcare provider for more information on a specific drug of interest.

Source: Pulito, Claudio, et al. “Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion.” Oncotarget 6.20 (2015): 18134.

Posted August 18, 2015.

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