Wednesday, 4 December 2013

Multiple myeloma – Treatments In Herbal medicine perspective

Multiple myeloma. also known as plasma cell myeloma or Kahler’s disease, is a types of abnormal growth of plasma cells collected in the none marrow where they grow and multiple to interfere with the production of normal blood cells. Paraprotein, an abnormal antibody produced by the plasma cell myeloma not only can cause kidney problem but also interference with the Roche automated total bilirubin assay caused by precipitate formation of that can cause clinical confusion, according to the study by the Harvard Medical School, Boston(1). Other study indicated that the production of paraproteins caused spurious results on individual analytes including total bilirubin (TBIL), direct bilirubin (DBIL), or HDL-cholesterol (HDL-C)(b). there is also a report of a 50 years old
chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM)(c).
VI. Treatments
B. In Herbal medicine perspective
1. Grape seed and skin
In the study to investigate whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma (MM) cells by interfering with NF-kappaB and STAT3 pathways, showed that resveratrol inhibited the proliferation of human multiple myeloma cell lines regardless of whether they were sensitive or resistant to the conventional chemotherapy agents. This stilbene also potentiated the apoptotic effects of bortezomib and thalidomide. Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products, including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT(68).
2. Cayenne
Capsaicin is a constituent of green and red peppers inhibited constitutive activation of STAT3 in multiple myeloma cells in a dose- and time-dependent manner, with minimum effect on STAT5. Capsaicin also inhibited the interleukin-6-induced STAT3 activation. The activation of Janus-activated kinase 1 and c-Src, implicated in STAT3 activation, was also inhibited by the vanilloid, with no effect on extracellular signal-regulated kinase 1/2 activation. Pervanadate reversed the capsaicin-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor. Finally, capsaicin induced the accumulation of cells in G(1) phase, inhibited proliferation, and induced apoptosis, as indicated by caspase activation. Capsaicin also significantly potentiated the apoptotic effects of Velcade and thalidomide in multiple myeloma cells. When administered i.p., capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male athymic nu/nu mice, according to the study by The University of Texas M. D. Anderson Cancer Center(69).
3. Tripterygium Wilfordi (Thunder of God vine) and Celastrus Regelii
Celastrola, is a remedial ingredient isolated from the root extracts of Tripterygium Wilfordi (Thunder of God vine) and Celastrus Regelii. According to the study by the National University of Singapore, celastrol inhibited the proliferation of MM cell lines regardless of whether they were sensitive or resistant to bortezomib and other conventional chemotherapeutic drugs. It also synergistically enhanced the apoptotic effects of thalidomide and bortezomib. This correlated with the down-regulation of various proliferative and anti-apoptotic gene products including cyclin D1, Bcl-2, Bcl-xL, survivin, XIAP and Mcl-1. These effects of celastrol were mediated through suppression of constitutively active NF-κB induced by inhibition of IκBα kinase activation; and the phosphorylation of IκBα and of p65. Celastrol also inhibited both the constitutive and IL6-induced activation of STAT3, which induced apoptosis as indicated by an increase in the accumulation of cells in the sub-G1 phase, an increase in the expression of pro-apoptotic proteins and activation of caspase-3(70).
4. Nigella sativa
Thymoquinone(TQ), is a phytochemical compound of the plant Nigella sativa. According to the study by the National University of Singapore, TQ inhibited both constitutive and IL-6-inducible STAT3 phosphorylation which correlated with the inhibition of c-Src and JAK2 activation. Vanadate reversed the TQ-induced down-regulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that TQ can induce the expression of Src homology-2 phosphatase 2 that correlated with suppression of STAT3 activation. TQ also down-regulated the expression of STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1 and vascular endothelial growth factor. Finally, TQ induced the accumulation of cells in sub-G1 phase, inhibited proliferation and induced apoptosis, as indicated by poly ADP ribose polymerase cleavage. TQ also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells.(71)
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Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/12521367
(b) http://www.ncbi.nlm.nih.gov/pubmed/18251580
(c) http://www.ncbi.nlm.nih.gov/pubmed/22073517
(68) http://www.ncbi.nlm.nih.gov/pubmed/17164350
(69) http://www.ncbi.nlm.nih.gov/pubmed/17505005
(70) http://www.ncbi.nlm.nih.gov/pubmed/21506956
(71) http://www.ncbi.nlm.nih.gov/pubmed/20880395

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