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At High Concentration, DS Elicits Apoptosis of Cancer Cells through Multiple Mechanisms

Apoptosis is a special form of cell death, also named programmed cell death. Dammarane sapogenins and derivatives may activate a series of enzymes inside cells in an orderly fashion and resulting in cancer death through activating apoptosis pathways.

The figure 1 shows, after 25ug/ml dammarane sapogenins treatment, a typical microphotograph of apoptotic cells, where clusters of small vesicles (apoptotic bodies) are seen in treated cancer cells.


Figure 1

Dammarane sapogenins and derivative compounds are effective against a very wide spectrum of cancer cell types. The pro-apoptotic effect of dammarane sapogenins has been demonstrated in various cancer cells:

Pancreatic cancer:  

BXPC-3, Capan-1, MIAPaCa

Breast cancer:

MCF7, MCF7adr, MDA435LCC6M, MDA435LCC6W

Brain cancer:

U87, U87delta, 9L, SF188, SF120, SF210, U126, U373

Prostate cancer:

LNCaP, PC3

Intestinal cancer:

HCT15

Gastric cancer:

Keto

Melanoma:

B16, MMRU, SK-mel-110

Lung cancer:

H460, MS-1, H838

Liver cancer:

H22

Sarcoma:

S180

Dammarane sapogenins induce cancer cell apoptosis through multiple mechanisms:

  • Activate caspases 3 & 8 (figure 2)
  • Inhibit Akt phosphorylation to shut down proliferative process (figure 3)
  • Increase intracellular free radical levels (figure 4)


Figure 2. Caspases 3 & 8 are two critical players in initiating apoptotic process. Dammarane sapogenins activate caspases 3 and 8 in a concentration-dependent manner.


Figure 3. The phosphorylation of Akt can trigger cells to initiate their proliferation process. However, dammarane sapogenins treatment dose-dependently reduce Akt phosphorylation.

Figure 4. Overproduction of intracellular free radicals can damage cell organelles, therefore induce cell apoptosis. Dammarane sapogenins stimulate free radical production does-dependently.

In summary, the pro-apoptotic mechanisms of dammarane sapogenins can be illustrated in following figures:

 
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