Black cumin seed for myeloma

Dr. Weeks Comment:  Black cumin seed – one of the potent ingredients in SOUL – the anti-inflammtory drink  -has proven to be a “promising” agent for people suffering with multiple myeloma.

“…TQ may represent a promising drug candidate for the treatment of patients with MM, providing a rationale for its clinical evaluation…”

Thymoquinone Inhibits the CXCL12-Induced Chemotaxis of Multiple Myeloma Cells and Increases Their Susceptibility to Fas-Mediated Apoptosis

Hossam M. Ashour, Editor
PLoS One. 2011; 6(9): e23741.
Published online Sep 1, 2011. doi:  10.1371/journal.pone.0023741

 

Abstract

In multiple myeloma (MM), malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus, we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12 resulted in the association of CXCR4 with CD45 and activation of PLCβ3, AKT, RhoA, IκBα and ERK1/2. Using siRNA-silencing techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone (TQ), the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4 expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation.

CONCLUSION

ur results showed that TQ treatment increases CD95-mediated, caspase-dependent apoptosis of MM cells by up to 85%. To our knowledge, we show here for the first time that TQ up-regulates CD95 expression on the surface of MM cells and increases their susceptibility to Fas-mediated apoptosis. Interestingly, Gali-Muhtasib et al.previously reported a pro-apoptotic activity of TQ treatment, though in a different cancer model (colorectal cancer cells) and involving a different mechanism of action (triggering the inactivation of the stress response pathway sensor CHEK1) [52]. Recently, Li et al. also reported that TQ inhibits the proliferation and induces the apoptosis of MM cells through the suppression of stat3 activation pathway [53].

In conclusion, the present data expand our knowledge of TQ mechanism of action and suggest that TQ may represent a promising drug candidate for the treatment of patients with MM, providing a rationale for its clinical evaluation.

 

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