Sea Cucumber Extract TBL-12 Correlative Studies on the Anticancer Effects

Multiple myeloma is a cancer that evolves from a state known as Monoclonal Gammopathy of Undetermined Significance (MGUS), defined by parameters of M spike and bone marrow. After evolution to myeloma, patients may be asymptomatic, that is, without any endorgan disease of hypercalcemia, renal insufficiency, and anemia or bone lesions. In asymptomatic myeloma (ASxM), there is no standard therapy. Thalidomide has been tried in patients with ASxM but with significant toxicity. Since natural agents are known to reduce toxicity while exerting chemopreventive effects, in this study we tested the chemopreventive effect of a new novel agent TBL-12 extracted from sea cucumber (Unicorn Pacific Corporation). To determine the anticancer effect of TBL-12, first we performed independent cytotoxicity assays using cell culture models.

Results:

Anti-proliferative effects of TBL-12: The cellular effects induced after 48h captured under a phase contrast microscope showed remarkable decrease in the cell viability. As shown in Figure 2A, we observed cell death showing nuclear condensation in both KMSI and ARP1 cells indicating that the cell death could be induced through the mechanisms of apoptosis or programmed cell death in a time and dose dependent manner (however, this preliminary observation has to be confirmed with further specific assays for apoptosis).

Part II: Current study

Based on the TBL-12 dose selected from our earlier studies we extended the analysis to determine whether similar cell growth inhibitory effects could be induced by TBL-12 in other human cancer cell types at the dose of 100ug/ml. To determine this we used another fast growing myeloma cell type MM1 as shown in Figure 3 and two other human cancer cell types that represents prostate cancer (PC-3), and human cervical cancer cell type Caski, which is also positive for human papillomavirus HPV-16. Our findings revealed that TBL-12 treatment (100ug/ml) inhibited MM1 (>50%) cell growth in a time-dependent manner.

Summary of the findings

The preliminary studies conducted in Part 1 (presented earlier) suggest that TBL-12 is effective in reducing myeloma cell growth in a dose dependent manner. In part II, an extended analysis of cytotoxicity assay did not reveal any necrotic effect at in vitro conditions using cervical (Caski) and metastatic prostate cancer (PC-3) cells, however reduced cancer cell growth determined by MTT and cell survival assays. Based on the cellular changes observed it seems that TBL-12 may induce damage to the cancer cell membrane, associated with cell cycle arrest and suppression of cell division. We observed a small % of cells that goes in to a programmed cell death in contrast to necrotic cell death. Our current findings are consistent with our earlier reports in that we found an effective LD 50 dose of 100ug/ml in ARP1 cells and 200ug/ml for KMSI. In MM1 myeloma cells we observed that 100ug/ml is effective in suppressing cell growth as determined by the less number of cells in the treatment. This concentration is also found to be effective in inhibiting prostate and cervical cancer cell growth by >50%. Although these correlative study findings from cell based assays support the anticancer effects of TBL-12, investigating the cellular changes induced by TBL-12 could reveal several molecular targets in different human cancer.

Studies in progress

Further studies focusing on the identification of specific molecular changes induced by TBL-12 including immunological, biochemical and metabolic pathways will reveal its potential effects and health benefits. Findings from several ongoing

 Amitabha Mazumder, MD and Bhagavathi A. Narayanan, PhD 

 TBL-12 is currently in clinical trial at NYUCI- PI: Amitabha Mazumder, MD 

To view the full research and test results open the pdf below.

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The Benefits

YOUR IMMUNE SYSTEM

This natural product, with no known side effects, that improves both your immune system and quality of life.

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The Research

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The first natural product to be granted orphan drug indication for the treatment of Multiple Myeloma by the FDA. Discover the findings from some of the best scientists in the world.

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TBL-12 is a natural product made out of marine ingredients, with no known side effects. All you need to do is melt the frozen product and consume your required dose daily.

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